It was reported that the rubber headpiece used for the Frankenstein monster make-up was very uncomfortable for Lon Chaney Jr. to wear. It sat directly on his forehead and he constantly complained. Once he asked for it to be removed. Angry and frustrated when no one listened, he ripped it off himself, tearing open a bloody gash in his forehead. Production on the film was shut down for a couple of days.
The exterior scenes shot in the fictional town of Visaria re-used the town square set from All Quiet on the Western Front (1930).
Lon Chaney Jr. was known for his hard-drinking ways. During production of this film, Chaney became inebriated while in full costume and got lost in the intricate mazes that were part of the laboratory sets. It took several minutes for him to find his way free. A similar incident occurred many years later when Chaney played the Frankenstein Monster on an episode of "Tales of Tomorrow." Once again, Chaney became intoxicated and mistakenly believed that the show's live telecast was the final dress rehearsal. For much of the performance, Chaney stumbled about, picking up breakaway props he was supposed to destroy and then setting them back down.
Four of the principal actors from Universal Pictures' The Wolf Man (1941), which had finished shooting just a few weeks before production began on this film, and which was released during production, also appeared in this movie. Lon Chaney Jr., Ralph Bellamy, Bela Lugosi, and Evelyn Ankers all also appeared in this film; with the exception of Lugosi, each portrays a character very similar to their roles in "The Wolf Man".