The boys' mothers each deliberately try to give them chickenpox from a sleepover at Kenny's, 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. Upon finding out, the boys plot revenge.
Shelly gets chickenpox, and is rushed to the hospital. Since she is twelve years old, the disease has a short but very risky effect on her health. However, if she was older, she would've been under more critical conditions. After Randy and Sharon discover how dangerous the disease is to older kids, they contact the other parents. The parents decide that the boys should get the disease while they're young.
Kenny gets chickenpox and the parents use this as an opportunity to have the other boys get it as well. Aware of how contagious the disease is, they arrange a sleepover at Kenny's house (as Kenny has the chicken pox at the time), and force the other boys to attend. So Stan, Kyle and Cartman spend the night with Kenny. While at the McCormick's house, Mrs. McCormick reveals that Stuart and Gerald used to be friends, but once Gerald was promoted and eventually became a lawyer, Stuart became poor. They couldn't connect with each other as much, since their lives were so different, and inevitably, they stopped speaking to each other.
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 Kenny's dad. 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 with the doctor. Kyle discovers that his parents lied to him and intended for him to get chickenpox. He runs away before Sheila can explain.
Gerald and Stuart's fishing trip goes horribly wrong. They get into a fight and return home. Meanwhile, the boys ask Chef for advice. They ask him how they can get revenge on their parents, and give them herpes. Chef tells them about Frida, an old prostitute, who may be willing to help them out for pay.
The boys talk to Frida and pay her to contaminate their parents' things so that they will get sick too. When she finishes, their parents find them. Then, Kyle finally gets chickenpox and faints on the ground.
Kyle awakes at Hells Pass Hospital, with the other boys. Their parents visit and explain why they tried to give them chickenpox. The boys then admit that they were the ones who gave their parents herpes. They all laugh over the whole situation until Kenny suddenly dies from chickenpox.