John Hora, who had previously worked as Joe Dante's cinematographer on all of his movies, was cast as Ozzie after Steven Spielberg suggested him to play the absent minded professor. Director Dante and producer Michael Finnell were very skeptical about that idea and Spielberg insisted that they give him a screen test to just to see and was cast after impressing Dante and Finnell.
All of the cells seen outside the pod were in fact made out of Jello according to Peter Kuran, the special effects supervisor.
This is the only film directed by Joe Dante to win an Academy Award. It won the Best Visual Effects award.
(at around 13 mins) Many people say Thelma & Louise (1991) has the first selfie in movie history. But right before Tuck Pendleton is shrunk and put in the syringe, he grabs a Polaroid camera and does a selfie with one of his coworkers. And even before that, Clark Griswold takes one in National Lampoon's European Vacation (1985).
Dennis Quaid and Meg Ryan met on the set of the film, and dated from there. The two later married on February 14, 1991, but divorced in 2001 after she had an affair.
Arthur Kane: (at around 56 mins) Arthur "Killer" Kane, bass player for the infamous New York Dolls makes an appearance as a passenger when the Cowboy is first seen in the airliner.
Joe Dante: (at around 20 mins) as the first employee in the Vectorscope Lab attacked by the techno-terrorists.
Joe Dante: [Looney Tunes Sound Effects] Sound effects lifted from classic Warner Bros. cartoons are used multiple times throughout the movie.