The boys' mothers each deliberately try to give them chickenpox from a sleepover at Kenny's house who has chickenpox, they do this to prevent the children from catching it at a later age where it can be worse or even deadly, the boys then plot revenge.
When Shelly Marsh, Stan Marsh's sister gets chickenpox, she is rushed into hospital. Since she is twelve years old, the disease has a short but very risky effect on her health, unlike it would be if she was younger. After Randy Marsh and Sharon Marsh discover how dangerous the disease is to older kids and contact the other parents. The mothers decide that the boys should get the disease while they're young.
After the sleepover, Stan and Cartman come down with chickenpox while Kyle has remained healthy. Kyle's parents organize another sleepover that night for Kyle. Kyle talks to his father about his friendship with Stuart McCormick. Sheila hears them and secretly organizes a fishing trip for Stuart and Gerald.
At Kenny's house, Kyle is forced to do many unusual things by Sheila in order for him to get chickenpox. After he comes down with it he overhears his mother on the phone to Dr. Doctor. Kyle discovers that his parents lied to him and intended for him to get chickenpox, and he runs away before Sheila can explain.
Gerald and Stuart's fishing trip goes horribly wrong, with them getting into a fight and returning home. Meanwhile, the Boys go to Chef and ask how they can get revenge and give herpes to their parents, since they tried to give the children chickenpox. The children still don't understand why they did it. Chef tells them about Frida, an old prostitute.
The boys talk to Frida and pay her to contaminate their parents' things (to the tune of the Monkees' song I'm a Believer) so that they will get sick too. When that is done, the parents find them and Kyle finally gets chickenpox and faints on the ground.
Kyle then wakes up at Hell's Pass Hospital (with Stan, Cartman and Kenny) where their parents visit and explain why they tried to give the boys chickenpox. The boys then admit that they were the ones who gave their parents herpes. They all end up laughing over the whole situation until Kenny suddenly dies from chickenpox.