Isaac Asimov was approached to write the novel from the script. He perused the script, and declared the script to be full of plot holes. Receiving permission to write the book the way he wanted, delays in filming and the speed at which he wrote saw the book appear before the film.
The scenes of crewmembers 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 50% greater speed than normal, then played back at normal speed.
As a college student, director Richard Fleischer was a pre-med student for a time.
When filming the scene where the other crew members remove attacking antibodies from Ms. Peterson for the first time, director Richard Fleischer allowed the actors to grab what they pleased. Gentlemen all, they specifically avoided removing them from Raquel Welch's breasts, with an end result that the director described as a "Las Vegas showgirl" effect. Fleischer pointed this out to the cast members - and on the second try, the actors all reached for her breasts. Finally the director realized that he would have to choreograph who removed what from where, and the result is seen in the final cut.
A now defunct thrill ride at Disney's Epcot Center, called Body Wars, was largely inspired by this film, even though it is not a Disney film. The director, Richard Fleischer, however, also directed Disney's first science fiction film, 20000 Leagues Under the Sea (1954).
The plot of this movie has partly been anticipated by (or been plagiarized from) the first season episode "I Dream of Jeannie: The Moving Finger (#1.9)" (1965). In that episode, Major Nelson works as technical consultant for a studio making a movie, in which an American astronaut, shrunken to the size of a pinhead, is injected into the bloodstream of a Soviet astronaut, works his way to the brain and retrieves information vital to the defense of the country.