The plot of this movie was partly borrowed for the first-season episode I Dream of Jeannie: The Moving Finger (1965). In that episode, Capt. 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. The screenplay to "Fantastic Voyage" was completed in 1964, from an original story that was written in 1963.
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, 20,000 Leagues Under the Sea (1954).
Isaac Asimov was approached to write the novel from the script. He perused the script and declared it 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.
In his book, special effects man L.B. Abbott writes about making use of a giant champagne glass built for another movie to fill with water and use for the whirlpool sequence when the ship is sucked through a tear in the artery. Althougth he doesn't mention the movie's name, it is most likely the film What a Way to Go! (1964) which had a sequence of Shirley MacLaine lounging in a giant champagne glass.
Original on-screen acknowledgment appearing after the end credits: "The makers of this film are indebted to the many doctors, technicians and research scientists, whose knowledge and insight helped guide this production."
The scenes in the spacious corridors of the secret CMDF medical facility were filmed in lower and upper concourses of the Los Angeles Memorial Sports Arena. Director Richard Fleischer would later use the arena for exteriors in Soylent Green (1973).
The jetliner seen in the opening of the film, a TWA 707 registration N746TW, had a long life and carried passengers from 1962-82. It was then mothballed at the Davis-Moncton storage facility and cannibalized for repair parts for the US Air Force fleet of KC-135 tankers. It was eventually scrapped.
Original on-screen prologue appearing immediately after the opening 20th Century-Fox logo and fanfare: "This film will take you where no one has ever been before; no eye witness has actually seen what you are about to see. But in this world of ours where going to the moon will soon be upon us and where the most incredible things are happening all around us, someday, perhaps tomorrow, the fantastic events you are about to see can and will take place."