diff --git a/.github/workflows/tests.yml b/.github/workflows/tests.yml
index 59c5c39fd4..f17e7f5ec1 100644
--- a/.github/workflows/tests.yml
+++ b/.github/workflows/tests.yml
@@ -21,17 +21,18 @@ jobs:
         - windows
         config:
         # [Python version, tox env]
-        - ["3.8",   "lint"]
+        - ["3.9",   "lint"]
         - ["3.6",   "py36"]
         - ["3.7",   "py37"]
         - ["3.8",   "py38"]
         - ["3.9",   "py39"]
-        - ["3.8",   "docs"]
-        - ["3.8",   "coverage"]
+        - ["3.10",  "py310"]
+        - ["3.9",   "docs"]
+        - ["3.9",   "coverage"]
         exclude:
-          - { os: windows, config: ["3.8",   "lint"] }
-          - { os: windows, config: ["3.8",   "docs"] }
-          - { os: windows, config: ["3.8",   "coverage"] }
+          - { os: windows, config: ["3.9",   "lint"] }
+          - { os: windows, config: ["3.9",   "docs"] }
+          - { os: windows, config: ["3.9",   "coverage"] }
 
     runs-on: ${{ matrix.os }}-latest
     name: ${{ matrix.os }}-${{ matrix.config[1] }}
diff --git a/.gitignore b/.gitignore
index f8055ebe90..5abcfe9ec0 100644
--- a/.gitignore
+++ b/.gitignore
@@ -1,9 +1,11 @@
 # Generated from:
 # https://github.com/zopefoundation/meta/tree/master/config/zope-product
+*.dll
 *.egg-info/
 *.profraw
 *.pyc
 *.pyo
+*.so
 .coverage
 .coverage.*
 .eggs/
diff --git a/.meta.toml b/.meta.toml
index 9da3b03d98..2fc292d66c 100644
--- a/.meta.toml
+++ b/.meta.toml
@@ -2,15 +2,15 @@
 # https://github.com/zopefoundation/meta/tree/master/config/zope-product
 [meta]
 template = "zope-product"
-commit-id = "10891b6cf9212ecd48f9bc70138aa14324d6a2b0"
+commit-id = "4b216b8aa60ef769d82827f7087507800a468972"
 
 [python]
-with-appveyor = false
 with-pypy = false
 with-legacy-python = false
 with-docs = true
 with-sphinx-doctests = false
 with-windows = true
+with-future-python = false
 
 [coverage]
 fail-under = 80
@@ -29,6 +29,9 @@ additional-config = [
     ]
 
 [tox]
+testenv-deps = [
+    "wheel",
+    ]
 additional-envlist = [
     "pre-commit",
     ]
diff --git a/CHANGES.rst b/CHANGES.rst
index 3ef50b0355..9bdbf0f6d0 100644
--- a/CHANGES.rst
+++ b/CHANGES.rst
@@ -8,8 +8,10 @@ The change log for the previous version, Zope 4, is at
 https://github.com/zopefoundation/Zope/blob/4.x/CHANGES.rst
 
 
-5.3.1 (unreleased)
-------------------
+5.4 (unreleased)
+----------------
+
+- Add support for Python 3.10.
 
 - Update to newest compatible versions of dependencies.
 
diff --git a/constraints.txt b/constraints.txt
index 40cf48ef6f..259ac9a95f 100644
--- a/constraints.txt
+++ b/constraints.txt
@@ -1,5 +1,5 @@
 AccessControl==5.2
-Acquisition==4.8
+Acquisition==4.9
 AuthEncoding==4.3
 BTrees==4.9.2
 Chameleon==3.9.1
@@ -12,18 +12,18 @@ Paste==3.5.0
 PasteDeploy==2.1.1
 Persistence==3.1
 Products.BTreeFolder2==4.3
-Products.ZCatalog==6.0
+Products.ZCatalog==6.1
 Record==3.5
-RestrictedPython==5.1
+RestrictedPython==5.2
 SecretStorage==3.3.1
-WSGIProxy2==0.4.6
+WSGIProxy2==0.5.1
 WebOb==1.8.7
-WebTest==2.0.35
+WebTest==3.0.0
 ZConfig==3.6.0
-ZEO==5.2.2
+ZEO==5.2.3
 ZODB==5.6.0
 Zope2==4.0
-cryptography==3.4.7
+cryptography==35.0.0
 five.localsitemanager==3.2.2
 funcsigs==1.0.2
 future==0.18.2
@@ -31,19 +31,19 @@ ipaddress==1.0.23
 jeepney==0.7.1
 mock==4.0.3
 multipart==0.2.4
-pbr==5.6.0
+pbr==5.8.0
 persistent==4.7.0
-pytz==2021.1
+pytz==2021.3
 roman==3.3
 shutilwhich==1.1.0
 six==1.16.0
 transaction==3.0.1
 waitress==2.0.0
 z3c.pt==3.3.0
-zExceptions==4.1
+zExceptions==4.2
 zc.lockfile==2.0
 zdaemon==4.3
-zodbpickle==2.0.0
+zodbpickle==2.2.0
 zope.annotation==4.7.0
 zope.browser==2.3
 zope.browsermenu==4.4
@@ -63,7 +63,7 @@ zope.dottedname==4.3
 zope.event==4.5.0
 zope.exceptions==4.4
 zope.filerepresentation==5.0.0
-zope.formlib==4.7.1
+zope.formlib==5.0.1
 zope.globalrequest==1.5
 zope.hookable==5.1.0
 zope.i18n==4.8.0
@@ -71,16 +71,16 @@ zope.i18nmessageid==5.0.1
 zope.interface==5.4.0
 zope.lifecycleevent==4.3.0
 zope.location==4.2
-zope.pagetemplate==4.5.0
+zope.pagetemplate==4.6.0
 zope.processlifetime==2.3.0
-zope.proxy==4.4.0
+zope.proxy==4.5.0
 zope.ptresource==4.2.0
 zope.publisher==6.0.2
 zope.ramcache==2.3
-zope.schema==6.1.0
+zope.schema==6.2.0
 zope.security==5.1.1
 zope.sendmail==5.2
-zope.sequencesort==4.1.2
+zope.sequencesort==4.2
 zope.site==4.5.0
 zope.size==4.3
 zope.structuredtext==4.3
@@ -88,6 +88,6 @@ zope.tal==4.5
 zope.tales==5.1
 zope.testbrowser==5.5.1
 zope.testing==4.9
-zope.testrunner==5.3.0
+zope.testrunner==5.4.0
 zope.traversing==4.4.1
 zope.viewlet==4.2.1
diff --git a/requirements-full.txt b/requirements-full.txt
index ee0a26cd84..9a55a88cee 100644
--- a/requirements-full.txt
+++ b/requirements-full.txt
@@ -1,6 +1,6 @@
 -e git+https://github.com/zopefoundation/Zope.git@master#egg=Zope
 AccessControl==5.2
-Acquisition==4.8
+Acquisition==4.9
 AuthEncoding==4.3
 BTrees==4.9.2
 Chameleon==3.9.1
@@ -13,18 +13,18 @@ Paste==3.5.0
 PasteDeploy==2.1.1
 Persistence==3.1
 Products.BTreeFolder2==4.3
-Products.ZCatalog==6.0
+Products.ZCatalog==6.1
 Record==3.5
-RestrictedPython==5.1
+RestrictedPython==5.2
 SecretStorage==3.3.1
-WSGIProxy2==0.4.6
+WSGIProxy2==0.5.1
 WebOb==1.8.7
-WebTest==2.0.35
+WebTest==3.0.0
 ZConfig==3.6.0
-ZEO==5.2.2
+ZEO==5.2.3
 ZODB==5.6.0
 Zope2==4.0
-cryptography==3.4.7
+cryptography==35.0.0
 five.localsitemanager==3.2.2
 funcsigs==1.0.2
 future==0.18.2
@@ -32,19 +32,19 @@ ipaddress==1.0.23
 jeepney==0.7.1
 mock==4.0.3
 multipart==0.2.4
-pbr==5.6.0
+pbr==5.8.0
 persistent==4.7.0
-pytz==2021.1
+pytz==2021.3
 roman==3.3
 shutilwhich==1.1.0
 six==1.16.0
 transaction==3.0.1
 waitress==2.0.0
 z3c.pt==3.3.0
-zExceptions==4.1
+zExceptions==4.2
 zc.lockfile==2.0
 zdaemon==4.3
-zodbpickle==2.0.0
+zodbpickle==2.2.0
 zope.annotation==4.7.0
 zope.browser==2.3
 zope.browsermenu==4.4
@@ -64,7 +64,7 @@ zope.dottedname==4.3
 zope.event==4.5.0
 zope.exceptions==4.4
 zope.filerepresentation==5.0.0
-zope.formlib==4.7.1
+zope.formlib==5.0.1
 zope.globalrequest==1.5
 zope.hookable==5.1.0
 zope.i18n==4.8.0
@@ -72,16 +72,16 @@ zope.i18nmessageid==5.0.1
 zope.interface==5.4.0
 zope.lifecycleevent==4.3.0
 zope.location==4.2
-zope.pagetemplate==4.5.0
+zope.pagetemplate==4.6.0
 zope.processlifetime==2.3.0
-zope.proxy==4.4.0
+zope.proxy==4.5.0
 zope.ptresource==4.2.0
 zope.publisher==6.0.2
 zope.ramcache==2.3
-zope.schema==6.1.0
+zope.schema==6.2.0
 zope.security==5.1.1
 zope.sendmail==5.2
-zope.sequencesort==4.1.2
+zope.sequencesort==4.2
 zope.site==4.5.0
 zope.size==4.3
 zope.structuredtext==4.3
@@ -89,6 +89,6 @@ zope.tal==4.5
 zope.tales==5.1
 zope.testbrowser==5.5.1
 zope.testing==4.9
-zope.testrunner==5.3.0
+zope.testrunner==5.4.0
 zope.traversing==4.4.1
 zope.viewlet==4.2.1
diff --git a/setup.py b/setup.py
index 2169044175..b1e7721995 100644
--- a/setup.py
+++ b/setup.py
@@ -29,7 +29,7 @@ def _read_file(filename):
 README = _read_file('README.rst')
 CHANGES = _read_file('CHANGES.rst')
 
-version = '5.3.1.dev0'
+version = '5.4.dev0'
 
 
 setup(
@@ -59,6 +59,7 @@ def _read_file(filename):
         "Programming Language :: Python :: 3.7",
         "Programming Language :: Python :: 3.8",
         "Programming Language :: Python :: 3.9",
+        "Programming Language :: Python :: 3.10",
         "Programming Language :: Python :: Implementation :: CPython",
         "Topic :: Internet :: WWW/HTTP :: Dynamic Content",
         "Topic :: Internet :: WWW/HTTP :: WSGI :: Application",
diff --git a/tox.ini b/tox.ini
index 63a5292cfd..74f7724804 100644
--- a/tox.ini
+++ b/tox.ini
@@ -8,6 +8,7 @@ envlist =
     py37
     py38
     py39
+    py310
     docs
     coverage
     pre-commit
@@ -18,6 +19,7 @@ skip_install = true
 deps =
     setuptools < 52
     zc.buildout
+    wheel
 commands_pre =
     {envbindir}/buildout -c {toxinidir}/buildout.cfg buildout:directory={envdir} buildout:develop={toxinidir} install alltests
 commands =
@@ -79,8 +81,6 @@ commands =
 [testenv:docs]
 basepython = python3
 skip_install = false
-# Until repoze.sphinx.autointerface supports Sphinx 4.x we cannot use it:
-deps = Sphinx < 4
 extras =
     docs
 commands_pre =
diff --git a/versions-prod.cfg b/versions-prod.cfg
index 5299ab5c27..1910a4d1b5 100644
--- a/versions-prod.cfg
+++ b/versions-prod.cfg
@@ -5,7 +5,7 @@
 Zope =
 Zope2 = 4.0
 AccessControl = 5.2
-Acquisition = 4.8
+Acquisition = 4.9
 AuthEncoding = 4.3
 BTrees = 4.9.2
 Chameleon = 3.9.1
@@ -18,17 +18,17 @@ Paste = 3.5.0
 PasteDeploy = 2.1.1
 Persistence = 3.1
 Products.BTreeFolder2 = 4.3
-Products.ZCatalog = 6.0
+Products.ZCatalog = 6.1
 Record = 3.5
-RestrictedPython = 5.1
+RestrictedPython = 5.2
 SecretStorage = 3.3.1
-WSGIProxy2 = 0.4.6
+WSGIProxy2 = 0.5.1
 WebOb = 1.8.7
-WebTest = 2.0.35
+WebTest = 3.0.0
 ZConfig = 3.6.0
-ZEO = 5.2.2
+ZEO = 5.2.3
 ZODB = 5.6.0
-cryptography = 3.4.7
+cryptography = 35.0.0
 five.localsitemanager = 3.2.2
 funcsigs = 1.0.2
 future = 0.18.2
@@ -36,16 +36,16 @@ ipaddress = 1.0.23
 jeepney = 0.7.1
 mock = 4.0.3
 multipart = 0.2.4
-pbr = 5.6.0
+pbr = 5.8.0
 persistent = 4.7.0
-pytz = 2021.1
+pytz = 2021.3
 roman = 3.3
 shutilwhich = 1.1.0
 six = 1.16.0
 transaction = 3.0.1
 waitress = 2.0.0
 z3c.pt = 3.3.0
-zExceptions = 4.1
+zExceptions = 4.2
 zc.lockfile = 2.0
 zdaemon = 4.3
 zodbpickle = 2.2.0
@@ -68,7 +68,7 @@ zope.dottedname = 4.3
 zope.event = 4.5.0
 zope.exceptions = 4.4
 zope.filerepresentation = 5.0.0
-zope.formlib = 4.7.1
+zope.formlib = 5.0.1
 zope.globalrequest = 1.5
 zope.hookable = 5.1.0
 zope.i18n = 4.8.0
@@ -76,16 +76,16 @@ zope.i18nmessageid = 5.0.1
 zope.interface = 5.4.0
 zope.lifecycleevent = 4.3.0
 zope.location = 4.2
-zope.pagetemplate = 4.5.0
+zope.pagetemplate = 4.6.0
 zope.processlifetime = 2.3.0
-zope.proxy = 4.4.0
+zope.proxy = 4.5.0
 zope.ptresource = 4.2.0
 zope.publisher = 6.0.2
 zope.ramcache = 2.3
-zope.schema = 6.1.0
+zope.schema = 6.2.0
 zope.security = 5.1.1
 zope.sendmail = 5.2
-zope.sequencesort = 4.1.2
+zope.sequencesort = 4.2
 zope.site = 4.5.0
 zope.size = 4.3
 zope.structuredtext = 4.3
@@ -93,6 +93,6 @@ zope.tal = 4.5
 zope.tales = 5.1
 zope.testbrowser = 5.5.1
 zope.testing = 4.9
-zope.testrunner = 5.3.0
+zope.testrunner = 5.4.0
 zope.traversing = 4.4.1
 zope.viewlet = 4.2.1
diff --git a/versions.cfg b/versions.cfg
index 63b992c3da..0714e4b91d 100644
--- a/versions.cfg
+++ b/versions.cfg
@@ -6,64 +6,64 @@ versions = versions
 [versions]
 # Version pins for development and optional dependencies.
 Babel = 2.9.1
-Jinja2 = 3.0.1
+Jinja2 = 3.0.3
 MarkupSafe = 2.0.1
-Pygments = 2.9.0
-Sphinx = 4.1.2
+Pygments = 2.10.0
+Sphinx = 4.3.0
 alabaster = 0.7.12
 appdirs = 1.4.4
 attrs = 21.2.0
-backports.entry-points-selectable = 1.1.0
+backports.entry-points-selectable = 1.1.1
 backports.functools-lru-cache = 1.6.4
-beautifulsoup4 = 4.9.3
-bleach = 3.3.1
+beautifulsoup4 = 4.10.0
+bleach = 4.1.0
 buildout.wheel = 0.2.0
-certifi = 2021.5.30
-cffi = 1.14.6
+certifi = 2021.10.8
+cffi = 1.15.0
 chardet = 4.0.0
-charset-normalizer = 2.0.4
+charset-normalizer = 2.0.7
 cmarkgfm = 0.6.0
 collective.recipe.cmd = 0.11
 collective.recipe.sphinxbuilder = 1.1
 collective.recipe.template = 2.1
 colorama = 0.4.4
-configparser = 5.0.2
+configparser = 5.1.0
 contextlib2 = 21.6.0
-coverage = 5.5
-distlib = 0.3.2
-# sphinx-rtd-theme 0.5.2 requires docutils <0.17
-docutils = 0.16
+coverage = 6.1.2
+distlib = 0.3.3
+# sphinx-rtd-theme 1.0.0 requires docutils <0.18
+docutils = 0.17
 entrypoints = 0.3
-filelock = 3.0.12
-idna = 3.2
-imagesize = 1.2.0
-importlib-metadata = 4.6.2
-keyring = 23.0.1
-lxml = 4.6.3
+filelock = 3.4.0
+idna = 3.3
+imagesize = 1.3.0
+importlib-metadata = 4.8.2
+keyring = 23.2.1
+lxml = 4.6.4
 manuel = 1.10.1
-more-itertools = 8.8.0
+more-itertools = 8.11.0
 mr.developer = 2.0.1
 nose = 1.3.7
-packaging = 21.0
+packaging = 21.3
 pathlib2 = 2.3.6
-pip = 21.2.2
-pkginfo = 1.7.1
-platformdirs = 2.2.0
+pip = 21.3.1
+pkginfo = 1.8.1
+platformdirs = 2.4.0
 plone.recipe.command = 1.1
-pluggy = 0.13.1
-py = 1.10.0
-pycparser = 2.20
-pyparsing = 2.4.7
+pluggy = 1.0.0
+py = 1.11.0
+pycparser = 2.21
+pyparsing = 3.0.6
 python-gettext = 4.0
-readme-renderer = 29.0
+readme-renderer = 30.0
 repoze.sphinx.autointerface = 0.8
 requests = 2.26.0
 requests-toolbelt = 0.9.1
 rfc3986 = 1.5.0
 scandir = 1.10.0
-snowballstemmer = 2.1.0
-soupsieve = 2.2.1
-sphinx-rtd-theme = 0.5.2
+snowballstemmer = 2.2.0
+soupsieve = 2.3.1
+sphinx-rtd-theme = 1.0.0
 sphinxcontrib-applehelp = 1.0.2
 sphinxcontrib-devhelp = 1.0.2
 sphinxcontrib-htmlhelp = 2.0.0
@@ -73,17 +73,17 @@ sphinxcontrib-serializinghtml = 1.1.5
 sphinxcontrib-websupport = 1.2.4
 tempstorage = 5.2
 toml = 0.10.2
-tox = 3.24.0
-tqdm = 4.62.0
-twine = 3.4.2
+tox = 3.24.4
+tqdm = 4.62.3
+twine = 3.6.0
 typing = 3.10.0.0
-urllib3 = 1.26.6
-virtualenv = 20.6.0
+urllib3 = 1.26.7
+virtualenv = 20.10.0
 webencodings = 0.5.1
-wheel = 0.36.2
+wheel = 0.37.0
 z3c.checkversions = 1.2
 zc.recipe.egg = 2.0.7
 zc.recipe.testrunner = 2.2
-zest.releaser = 6.22.1
-zipp = 3.5.0
+zest.releaser = 6.22.2
+zipp = 3.6.0
 zodbupdate = 1.5