Although they had both previously appeared in Hamlet (1948) and Moulin Rouge (1952), Christopher Lee and Peter Cushing met on the set of this film for the first time. They would pass the time between shots by exchanging Looney Tunes phrases, and quickly developed a fast friendship, which lasted until Cushing's death in 1994.
The script called for a child actress to play Hazel Court's character, Elizabeth, as a little girl of three or four in flashback scenes. Court suggested to the producers that her daughter, Sally Walsh, who looked very much like her mother, play the part. As Court said in an interview, "She hated it - HATED being in it! I think it was all foreign to her, and she didn't understand it. She still remembers it to this day, and still doesn't like it!"
Christopher Lee's monster make-up was almost literally done at the "last minute". After previous attempts to design a monster make-up using a cast of Lee's head had failed, make-up artist Philip Leakey made the final design the day before shooting began, directly onto Lee's face, using primarily cotton and other household materials. Since he didn't use any latex or molds, the make-up had to be recreated from scratch every day.
Christopher Lee and Peter Cushing's friendship was sparked when Lee stormed into Cushing's dressing room, complaining that "I've got no lines!" Cushing kindly responded, "You're lucky. I've read the script."
The idea originated with Milton Subotsky, who went on to co-found Amicus Films, Hammer's main rival during the 1960s and early 1970s. The script was revised several times to avoid repeating any elements from the Universal Frankenstein series. As part of this effort, new monster make-up had to be devised especially for this film.
The original concept for this film was a black-and-white feature with Boris Karloff as the Frankenstein monster. Universal threatened a lawsuit if Hammer copied any elements from the classic Universal version. Hammer had Jimmy Sangster completely redo the script and had Jack Asher shoot it in Eastmancolour.
The painting on the staircase shown to Professor Bernstein is Rembrandt's 1632 The Anatomy Lesson Of Dr Nicolaes Tulp. Mirroring Victor's own actions is shows the dissection of a hanged criminal, in this case armed robber Aris Kindt.