Originally, the University of Arizona used in the movie agreed to let filming take place there but changed their minds after they read the script, they eventually changed their minds again and permitted filming and also allowed the filmmakers to use some of their own students as extras.
Several scenes in this movie were not even in the script. The actors were told by the directors to improvise as they were filming. A couple of examples include the scene in the gym where Booger and Takashi are playing poker and the scene at the party when Poindexter puts his hand in the blender.
To test the effectiveness of their "nerd" makeup and wardrobes, Robert Carradine and Anthony Edwards attended a college rush-week, when real fraternities were reviewing prospective pledges (wanna-be members). The fraternity leader of the first house took one look at them both and said, "No way!"
The film deleted a subplot of the Nerds visiting the Tri-Lambda national conference in Las Vegas, in which the Nerds are outcasts and in which Gilbert talks to his uncle at the hotel where the conference is being held. These deleted scenes can be found on the "Panty Raid Edition" DVD.