Hugh Hefner was originally going to be in the Tromadu segment. There was even a shot of him saying, "Only the Toxic Avenger knows for sure!" in the original teaser trailer. Unfortunately, a cease-and-desist order from Hefner's lawyers forced Troma to remove any and all visual depictions of him from both their advertising and the final film. By all accounts, Hefner himself was initially fine with being in the film, but his lawyers convinced him he was unfairly coerced into being in the movie. Because of this, during the "Special Thanks To" sequence of the final credits, there's a special "No thanks to Hugh Hefner's lawyers" credit.
Before the film's world premiere, a decision was made to leave the World Trade Center in the opening narration despite the 9/11 attacks taking place a month earlier. This decision was applauded by the crowd.
Celeste Octavia (Kinky Finkelstein's assistant) offered to do her role completely nude in exchange for one line in the film, where she asks the doctor if it's time to remove the thermometer from her butt.
The now classic stock footage of the car-flip stunt from Sgt. Kabukiman N.Y.P.D. (1990) is used once again for this film. This footage has also been used for several other films including Terror Firmer (1999), and Tromeo and Juliet (1996).
The narration in the beginning and the ending was by Stan Lee. He is credited as Peter Parker.
Mitch Cohen: , who played Toxie in the original The Toxic Avenger (1984), as a racist who is lynched by the KKK after Toxie gives him a black-face treatment with a car engine.
Eli Roth: Fellow Director, Producer, and Actor is standing next to Lemmy Kilmeister outside the school in several scenes.