Cheech and Chong meet up by chance on the highway somewhere in California. They go in search of some dope and are accidentally deported to Mexico where in their desperation to get home they agree to drive a van back to the States so they can get back in time for a gig they are due to play. Unaware of the properties from which the van is constructed they make their way back having aquired a couple of female hitch-hikers whilst all the time avoiding the cops whom they are not even aware are following them.
Cheech must deal with losing his job, his angry neighbor, and trying to score with sexy Donna. Meanwhile, Chong meets Cheech's cousin Red and the two have a wild time in Hollywood with a big bag of buds and a cool Ferrari. Along the way they meet everyone from Pee Wee Herman to really cool aliens.
Cheech and Chong work briefly as car wash attendants and musicians before being hired to drive a car from Chicago to Las Vegas. Unbeknownst to them, their employers (themselves in double roles) have concealed five million dollars of dirty money in the upholstery. A series of adventures ensues, including the making of a porn film featuring 'The Guys' and their real-life squeezes.
Cheech & Chong are invited to a celebrity party/festival in Amsterdam. When they get there, however, it turns out that the guy who invited them has taken off with all the money, and the rest of the hosts have a VERY limited budget. They are actually expecting Burt Reynolds and Dolly Parton, so our heroes gets to be Mr. Burt and Mr. Dolly. We follow them around Amsterdam, at their hotel, (still) smokin' joints and doing shows.