Because Fry has flashbacks of himself and his Dad going ice fishing in 1988, the Planet Express crew go ice fishing. They don't have much luck, and after a whole day of no bites, they go back to the headquarters with only a baby fish - and a common cold. Professor Farnsworth explains that the common cold had been extinct for more than 500 years. Soon after, a quantine shield is put on top of the Planet Express building, and everyone (except Bender) catches the cold. Although Bender is needed to help the others during their illness, he escapes with germs on his hands, caught from Zoidberg accidentally sneezing on him. He then congratulates the quarantine crew, shaking their hands, and giving them the germs. The quarantine crew soon catches the cold, and there is a new outbreak.
After 99% of the city gets the cold, a bigger quantine shield is put on the city, which is then lifted physically out of the ground. Using tractor beams, the island of Manhatten is carried towards the Sun, towed by the starship Nimbus. The professor says that developing a vaccine is possible, but it requires the unmutated 20th century cold virus which only Fry has. As Fry is attached to a machine, preparing to be sliced gruesomely into a thin paste (to obtain a sample of the virus), he has a flashback of a high school science contest that he had entered. One of the other children won and his entry (A common cold virus contained in Fry's pet hamster) was sent into space.
In the future, Fry remembers this and stops himself from being pureed. Fry recalls that the experiment was shot into space, and the crew will need to escape the spaced and plastic-wrapped island to find it. As they shoot at the quantine shield, and by extension the Nimbus, Zapp Brannigan predictably shoots back, creating a hole in the shield with a powerful explosion. The crew finds the experiment and the Professor is able to engineer a vaccine.
At the end of the episode Fry has a flashback, showing him and his father in the ice fishing shack after he gets pulled out of the ice by his father. Fry and his father talk, and during the conversation his father shows one of the first, if not the only, signs of love towards Fry in the series. Fry's father offers him a beer, which Fry accepts. Fry then takes a drink of the beer and gives it back to his father.