Medical schools, at least as late as the 1980s, showed clips from this movie to illustrate various concepts in human anatomy, physiology, and especially immunology.
When filming the scene where the other crew members remove attacking antibodies from Raquel Welch for the first time, director Richard Fleischer allowed the actors to grab what they pleased. Gentlemen all, they specifically avoided removing them from Welch's breasts, with an end result that Fleischer described as a "Las Vegas showgirl" effect. He pointed this out to the cast members - and on the second try, the actors all reached for her breasts. Finally, Fleischer realized that he would have to choreograph who removed what from where, and the result is seen in the final cut.
The time spent in the movie of the crew once they are miniaturized takes up almost exactly one hour of the movie.
During filming, one of the two three-inch "Proteus" models used in the miniaturization sequence was left by an open window and was subsequently carried off by a crow.
The scenes of crew members swimming outside the sub were shot on dry soundstages with the actors suspended from wires. There was some additional hazard involved because, to avoid reflections from the metal, the wires were washed in acid to roughen them, which made them more likely to break. To create the impression of swimming in a resisting medium, the scenes were shot at fifty percent greater speed than normal, then played back at normal speed.