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Stratholme was the second largest human city in Lordaeron, matched only by the capital. At the beginning of the Second War, Stratholme, specifically the Alonsus Chapel, was the location where the Archbishop Alonsus Faol founded the holy Order of the Knights of the Silver Hand, and indoctrinated its first five members, including Uther the Lightbringer. In its glory days, it housed nearly 25,000 people, and included many well known buildings, from the glorious keep to Fras Siabi's famous tobacco shop.
Just before the Third War the Plague reached Stratholme in infected shipments of grain, most likely from Andorhal. The populace, unaware of the plague, baked and consumed the infected grain. Soon after, as the first undead started to rise, Prince Arthas and a contingent of soldiers arrived at Stratholme, but realized that the city had already been infected. Arthas thought that the only way of saving the city from the Plague was to cull all of the citizens inside. Most of the soldiers, including Uther the Lightbringer and Jaina Proudmoore chose not to help Arthas, thinking his purge was madness. Arthas and some soldiers, however, went on, and the city's population was almost completely massacred by them, along with the undead.
Stratholme was later taken under the control of the Undead Scourge. After the end of the war, when Arthas was called back to Northrend, the lich overlord Kel'Thuzad established Stratholme as his capital and positioned his floating fortress, the Necropolis Naxxramas, above the ruined city.