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Bud "Squirrel" Macintosh (Pauly Shore) and Doyle "Stubs" Johnson (Stephen Baldwin) are best friends and live together in the same house. Their girlfriends, Monique (Joey Lauren Adams) and Jen (Teresa Hill) are environmentalists who ask Bud and Doyle to join them at an Earth Day event. The troublemakers, however, are not interested in picking up trash, so they fake an injury to Doyle's head in order to get out of the environmentalist gathering. Although they are sympathetic at first, their girlfriends eventually find out it is a trick and go to the Earth Day event without Bud and Doyle. Once there, they call the boys from a payphone to announce they'll be joining some hot guys from a swim team at a party down by a lake. Jealous, Bud and Doyle drive out to the lake, only to find there is no party, and they have been had.
 
On the way home, they drive by an area where scientist Dr. Noah Faulkner (William Atherton) is about to seal his team into the "Bio-Dome" for a year without outside contact. Mistaking it for a mall and going inside to use the bathroom, they get sealed in along with the scientists. Dr. Leaky (Henry Gibson) discovers them and demands that they be kicked out. Faulkner refuses, claiming it would destroy the purpose of the experiment, so Bud and Doyle end up remaining. This proves a mistake, as Bud and Doyle begin acting like they did outside of the Dome, harming themselves and destroying many of the scientists' projects. The scientists remain silent, but they soon grow tired of the childish behavior and dump the boys into their desert environment section. After three days of being stuck in the desert environment, they discover a key in the lock of one of the windows and escape the Bio-Dome.
 
To impress their girlfriends with their newfound interest in the environment, Bud and Doyle organize a party at the Bio-Dome, but this only angers their girlfriends, who tell them they're destroying the Dome's experiment. After the party, Bud and Doyle try to make it up to their girlfriends by cleaning up all the trash, saving the Dome's environment, with the help of all the scientists. Faulkner, who has gone mad because of Bud and Doyle's antics, plans to blow up the Dome with homemade coconut bombs. He fails, but does blow open the Dome's door, allowing everyone to exit, considering the fiasco a success. The film ends with Faulkner running off into the desert after climbing out the same window Bud and Doyle used to escape through earlier, while Bud, Doyle, and their girlfriends drive off toward a mysterious factory so Doyle can yet again use the bathroom.