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BackgroundDr. Mephesto hadn't been seen since "Cartman Joins NAMBLA" until the Season 14 episode, "201". In "201", the appearance of the ranch is heavily revised, and also boarded up with a large door with a peephole and multiple locks. It is revealed that Dr. Mephesto, likely due to the failure of his experiments, has become a recluse, trying to be "left alone". He refuses to allow a black man (Mitch Conner in disguise) in after a car crash (although he does give directions to a gas station) until he is accused of racism.
It is unknown if Terrance Mephesto lives with his father there, as he is not present in many of the ranch's appearances. It is possible his mother has custody.
Kyle wants to genetically engineer a pot-bellied elephant; a mix between elephant and a pot-bellied pig; by using Kyle's Elephant and Cartman's pig, Fluffy. Kyle goes to the South Park Genetic Engineering Ranch to make a pot-bellied elephant but sadly, figures out pig and elephant genes just won't splice. Dr. Mephesto takes a sample of Stan's blood to help Terrance, his son, make a human clone.
Dr. Mephesto brings Chef into the ranch to show him the turkey DNA he used to make turkeys that went horribly wrong, claiming he knew only Chef would believe him.
The people of South Park are seen at the ranch in the recap of the last episode and when Terrance and Phillip are watching American television.
Dr. Mephesto is shot at the ranch and is taken to the hospital. At the end of the episode Dr. Mephesto announces that Liane Cartman is actually a hermaphrodite which means she is Cartman's father. This is of course a cover up for the Denver Broncos as revealed in the episode "201".
Dr. Mephesto used the ranch to hold Larry.
Dr. Mephesto's ranch is used as the place where Hope(Junjun) gives birth.
Stan goes to the ranch and asks Dr. Mephesto for hormones so he can get his "period".
Cartman goes to the ranch and asks Dr. Mephesto to make him a mature friend, Dr. Mephesto says it's not that simple but if he wants to he could join NAMBLA (North American Marlon Brando Look Alikes) which Cartman mistakes for the other NAMBLA (North American Man Boy Love Association).
Cartman goes to the ranch and asks Dr. Mephesto to tell him who his real father is and Stan, Kyle and Kenny want him to clone Mohammed.