diff --git a/NEWS b/NEWS
index 0736609..8784ca0 100755
--- a/NEWS
+++ b/NEWS
@@ -1,6 +1,10 @@
 Changes in version 2.2.0
 ------------------------
 
+NEW FEATURES
+    o Added chunks parameter to Coverage.R and calculateBamCoverageByInterval
+      to reduce memory usage (#218)
+
 SIGNIFICANT USER-VISIBLE CHANGES
 
     o When base quality scores are found in the VCF, they are now used to
diff --git a/R/calculateBamCoverageByInterval.R b/R/calculateBamCoverageByInterval.R
index 24c304d..0d8dec1 100644
--- a/R/calculateBamCoverageByInterval.R
+++ b/R/calculateBamCoverageByInterval.R
@@ -16,6 +16,8 @@
 #' @param index.file The bai index. This is expected without the .bai file
 #' suffix, see \code{?scanBam}.
 #' @param keep.duplicates Keep or remove duplicated reads.
+#' @param chunks Split \code{interval.file} into specified number of chunks
+#' to reduce memory usage.
 #' @param ... Additional parameters passed to \code{ScanBamParam}.
 #' @return Returns total and average coverage by intervals.
 #' @author Markus Riester
@@ -39,36 +41,56 @@
 #'             scanBam scanFa scanFaIndex TabixFile
 calculateBamCoverageByInterval <- function(bam.file, interval.file,
     output.file = NULL, index.file = bam.file, keep.duplicates = FALSE,
-    ...) {
-    intervalGr <- readIntervalFile(interval.file, strict = FALSE,
+    chunks = 20, ...) {
+    intervalGrAll <- readIntervalFile(interval.file, strict = FALSE,
         verbose = FALSE)
+    # skip splitting with small panels
+    if (is.null(chunks) || is.na(chunks) || chunks < 2 ||
+        length(intervalGrAll) < chunks * 50) {
+        chunkIds <- rep(1, length(intervalGrAll))
+    } else {
+        chunkIds <- cut(seq_along(intervalGrAll), chunks, labels = FALSE)
+    }
+    .calculateBamCoverageByInterval <- function(intervalGr, ...) {
+        param <- ScanBamParam(what = c("pos", "qwidth", "flag"),
+                    which = intervalGr,
+                    flag = scanBamFlag(isUnmappedQuery = FALSE,
+                                 isNotPassingQualityControls = FALSE,
+                                 isSecondaryAlignment = FALSE,
+                                 isDuplicate = NA
+                         ),
+                    ...
+                 )
 
-    param <- ScanBamParam(what = c("pos", "qwidth", "flag"),
-                which = intervalGr,
-                flag = scanBamFlag(isUnmappedQuery = FALSE,
-                             isNotPassingQualityControls = FALSE,
-                             isSecondaryAlignment = FALSE,
-                             isDuplicate = NA
-                     ),
-                ...
-             )
+        xAll <- scanBam(bam.file, index = index.file, param = param)
+        xDupFiltered <- .filterDuplicates(xAll)
 
-    xAll <- scanBam(bam.file, index = index.file, param = param)
-    xDupFiltered <- .filterDuplicates(xAll)
+        x <- xDupFiltered
+        if (keep.duplicates) x <- xAll
 
-    x <- xDupFiltered
-    if (keep.duplicates) x <- xAll
+        intervalGr$coverage <- vapply(seq_along(x), function(i)
+            sum(coverage(IRanges(x[[i]][["pos"]], width = x[[i]][["qwidth"]]),
+                shift = -start(intervalGr)[i], width = width(intervalGr)[i])), integer(1))
 
-    intervalGr$coverage <- vapply(seq_along(x), function(i)
-        sum(coverage(IRanges(x[[i]][["pos"]], width = x[[i]][["qwidth"]]),
-            shift = -start(intervalGr)[i], width = width(intervalGr)[i])), integer(1))
+        intervalGr$average.coverage <- intervalGr$coverage / width(intervalGr)
 
-    intervalGr$average.coverage <- intervalGr$coverage / width(intervalGr)
+        intervalGr$counts <- as.numeric(vapply(x, function(y) length(y$pos), integer(1)))
+        intervalGr$duplication.rate <- 1 -
+            vapply(xDupFiltered, function(y) length(y$pos), integer(1)) /
+            vapply(xAll, function(y) length(y$pos), integer(1))
+        intervalGr    
+    }
+    intervalGrAll <- split(intervalGrAll, chunkIds)
 
-    intervalGr$counts <- as.numeric(vapply(x, function(y) length(y$pos), integer(1)))
-    intervalGr$duplication.rate <- 1 -
-        vapply(xDupFiltered, function(y) length(y$pos), integer(1)) /
-        vapply(xAll, function(y) length(y$pos), integer(1))
+    intervalGr <- unlist(GRangesList(
+        lapply(seq_along(intervalGrAll), function(i) {
+            if (length(intervalGrAll) > 1) {
+                flog.info("Processing %s (%i/%i)...", as.character(intervalGrAll[[i]][1]),
+                    i, length(intervalGrAll))
+            }
+            .calculateBamCoverageByInterval(intervalGrAll[[i]], ...)
+        }
+    )))
 
     if (!is.null(output.file)) {
         .writeCoverage(intervalGr, output.file)
diff --git a/inst/extdata/Coverage.R b/inst/extdata/Coverage.R
index f84a900..14ce923 100644
--- a/inst/extdata/Coverage.R
+++ b/inst/extdata/Coverage.R
@@ -25,6 +25,9 @@ option_list <- list(
     make_option(c("--out-dir"), action = "store", type = "character", 
         default = NULL,
         help = "Output directory to which results should be written"),
+    make_option(c("--chunks"), action = "store", type = "integer",
+        default = formals(PureCN::calculateBamCoverageByInterval)$chunks, 
+        help = "Split intervals into specified number of chunks to reduce memory usage [default %default]"),
     make_option(c("--parallel"), action = "store_true", default = FALSE,
         help = "Use BiocParallel to calculate coverage in parallel whem --bam is a list of BAM files."),
     make_option(c("--cores"), action = "store", type = "integer", default = 1,
@@ -132,6 +135,7 @@ getCoverageBams <- function(bamFiles, indexFiles, outdir, interval.file,
             PureCN::calculateBamCoverageByInterval(bam.file = bam.file,
                 interval.file = interval.file, output.file = output.file,
                 index.file = index.file, keep.duplicates = keep.duplicates,
+                chunks = opt$chunks,
                 mapqFilter = if (remove_mapq0) 1 else NA)
         }
         output.file
diff --git a/man/calculateBamCoverageByInterval.Rd b/man/calculateBamCoverageByInterval.Rd
index 7d62e7a..2a62d84 100644
--- a/man/calculateBamCoverageByInterval.Rd
+++ b/man/calculateBamCoverageByInterval.Rd
@@ -10,6 +10,7 @@ calculateBamCoverageByInterval(
   output.file = NULL,
   index.file = bam.file,
   keep.duplicates = FALSE,
+  chunks = 20,
   ...
 )
 }
@@ -27,6 +28,9 @@ suffix, see \code{?scanBam}.}
 
 \item{keep.duplicates}{Keep or remove duplicated reads.}
 
+\item{chunks}{Split \code{interval.file} into specified number of chunks
+to reduce memory usage.}
+
 \item{...}{Additional parameters passed to \code{ScanBamParam}.}
 }
 \value{
diff --git a/vignettes/Quick.Rmd b/vignettes/Quick.Rmd
index b863193..ee158b2 100755
--- a/vignettes/Quick.Rmd
+++ b/vignettes/Quick.Rmd
@@ -733,9 +733,10 @@ Argument name      | Corresponding PureCN argument | PureCN function
 `--intervals`      | `interval.file`  | `correctCoverageBias` 
 `--method`         | `method`  | `correctCoverageBias`
 `--keep-duplicates` | `keep.duplicates`  | `calculateBamCoverageByInterval`
-`--remove-mapq0`    | `mapqFilter`  | `ScanBamParam`
-`--skip-gc-norm`     | | `correctCoverageBias`
-`--out-dir`         | | 
+`--chunks`         | `chunks`  | `calculateBamCoverageByInterval`
+`--remove-mapq0`   | `mapqFilter`  | `ScanBamParam`
+`--skip-gc-norm`   | | `correctCoverageBias`
+`--out-dir`        | | 
 `--cores`          | | Number of CPUs to use when multiple BAMs are provided 
 `--parallel`       | | Use default `r Biocpkg("BiocParallel")` backend when multiple BAMs are provided 
 `--seed`           | |