Kyle is ill and missing from school, the boys think he's faking it. Mr. Garrison is also missing from school and the boys have fun with the substitute. Due to the previous week's activities regarding sex with small children and his somewhat substantial police record, Mr. Garrison is advised by the school board to take some time off. Kyle needs a kidney transplant, but his mother through the advice of Sharon Marsh seeks alternative holistic treatments from Miss Information, the woman who runs a new age store. Mr Mackey advises Mr. Garrison to use his free time to do something he's always wanted to do. Since Mr. Garrison has always wanted to write a novel and his is allegedly a big fan of poon-tang, Mr Mackey suggests that he write a great romance novel. Miss Information suggest that Kyle start taking a mixture of herbs (lemon juice and cayenne pepper) to help his body flush out the toxins making him sick. Mr. Garrison starts to write his penis laden romance novel, but gets writer's block when he encounters a nipple. Miss Information stops by the Broflovski house, to spin some more of her holistic mumbo-jumbo. Stan finds out from the doctor that the only person in South Park who has a kidney that could be transplanted into Kyle is Eric Cartman.
Stan brings Kyle over to meet with Cartman, who has a price for his kidney, $10 million. Two "native" Americans stop by Miss Information's shop to get rid of more of their junk, which the new age crazy citizens of South Park are eager to buy. One of the items is a "Cherokee Hair Tampon." Miss Information offers their service as holistic healers to Kyle's mother, who sets an appointment for the following day. Stan sees his friend dying and is beside himself while their parents have new age blinders on. Mr. Garrison starts writing a lesbian love scene in his novel, which quickly gives way to numerous mentions of penises. Stan, Kenny, Butters and Timmy go to Cartman's house, with the plan to take one of Cartman's kidneys. A live action commercial airs for "Cherokee Hair Tampons."
Cartman thwarts their plan with a "Kidney Blocker 2000." Mr. Garrison meets with the publishers at Harlequin Romances. They aren't interested in his romance novel as it contains the word penis in it 6,083 times and they consider it gay. Stan is depressed about the inevitable loss of his friend; however, Kenny isn't as sympathetic. At the new age shop, the two "native" Americans take one look at Kyle and they of course immediately recommend that Kyle see a real doctor. The citizens of South Park begin trashing the new age store. Stan tricks Cartman into thinking that he has lost his kidney, which gets him to sign a release for one of the two kidneys he still has.
Post transplant surgery Kyle is doing much better. Cartman; however, is pissed off that he lost his kidney. Mr. Garrison finds everyone at the hospital and has an announcement to make. He is not going to be their teacher anymore, it seems Harlequin Romances after hearing his argument about how women like reading only the penis part of romance novels, must have reconsidered, because they publish the novel "In the Valley of Penises" and it becomes a best seller.
Kenny dies when a piano falls on top of him; right after he gets pissed off with Stan, and tells him to screw himself, he's going home. Stan never notices.