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Dr. Alphonse Mephesto created genetically-altered turkeys for Thanksgiving but they escaped from his lab and began rampaging through South Park. The turkeys destroyed several structures, including Mr. Garrison's classroom, and murdered several townsfolk at Stark's Pond.
Dr. Mephesto attempted to warn Mayor McDaniels, but she dismissed his claims, citing Mephesto for being crazy. The turkeys are later seen rampaging a canned food drive near the South Park Library.
In an attempt to get the turkeys under control, Chef leads the townsfolk in a battle dressed as William Wallace, from the movie Braveheart. During the debacle, Kenny McCormick is killed by the turkeys. Eventually the townspeople are able to kill them all. The FBI soon arrives to escort Starvin' Marvin back to Ethiopia, with turkeys to feed his tribe.
The mutant turkeys resemble regular turkeys, only larger and having a much meaner demeanor.
- The Mutant Turkeys made a comeback in the South Park video game, where they serve as the main enemies in the level 'Operation: Turkey Butt', and minor enemies in later levels.