Silas (METHOD MAN) is known as the medicine man in his Staten Island neighborhood where he concocts all sorts of herb and drug-based remedies for any and all maladies. His friend Ivory (CHUCK DAVIS) thinks he should attend college, but doesn't get the chance himself when he's killed in a freak accident. In honor of his friend, Silas plants some cannabis in his ashes.
Jamal (REDMAN), on the other hand, is less industrious and lives in Jersey where his mother constantly badgers him to graduate from college, something that seems unlikely since he's spent the last six years at a two-year community college.
The two young men meet in a parking lot before taking some college entrance tests and smoke the pot grown in Ivory's ashes. With Ivory's ghost appearing and claiming he has "their back," the two take and ace the tests. Suddenly, everyone wants them to attend their colleges, including Harvard's Chancellor Huntley (FRED WILLARD) and Dean Cain (OBBA BABATUNDÉ).
The latter soon finds that was a mistake as he sees the two stoners clash with the university's austere atmosphere. Disrespectful of him and most everyone else, Silas and Jamal set out to have fun and get high all of the time, something that infuriates Bart (CHRIS ELWOOD), the captain of the crew team, especially when Silas starts hitting on his girlfriend, Lauren (LARK VOORHIES).
Jamal, on the other hand, is interested in Jamie (ESSENCE ATKINS), the spirited daughter of the Vice President of the U.S. (JEFFREY JONES). As the two men are accompanied by their mute friend, I Need Money (AL SHEARER), interact with their classmates including Jeffrey (JUSTIN URICH) and Tuan (TRIEU TRAN), and infuriate the university's unofficial "hall monitor," Gerald (T.J. THYNE), they continue smoking pot, having a good time ruffling feathers and acing their tests thanks to their special pot.
Yet, when it finally runs out, the two men must figure out what to do to prevent being kicked out of Harvard, all while dealing with an angry pimp, Baby Powder (MIKE EPPS), and the crew coach (HECTOR ELIZONDO), who wants to spite Bart. As they continue to pursue Lauren and Jamie, Silas tries to come up with some sort of herbal breakthrough that will impress Professor Wood (TRACEY WALTER) and thus keep them in school.