Cinematographer John Mescall's drinking had become so problematic that the studio had to provide a car to get him safely to and from the set. James Whale liked that he worked fast and rarely wasted time fussing with incidental camera and lighting hardware. He was still very good at his job, even when drunk.
Jack P. Pierce altered the make-up of Frankenstein's monster from this film's predecessor to reflect that he had survived the mill fire at the end of El doctor Frankenstein (1931) with some flesh burns and with much of his hair singed off.
Marilyn Harris, who played Maria, the girl The Monster accidentally kills in the original El doctor Frankenstein (1931), appears uncredited as another young girl. She is the leader of the group of young schoolgirls who encounter the Monster as he runs away from the blind man's burning house. Director James Whale deliberately gave her a one-word line ("Look!"), so she would be paid more by the studio as an actor with a speaking role, instead of as an extra.
Boris Karloff protested against the decision to make The Monster speak, but was overruled. Since he was required to speak in this film, Karloff was not able to remove his partial bridgework as he had done to help give the Monster his sunken cheek appearance in the first El doctor Frankenstein (1931). That's why The Monster appears fuller of face in the sequel.
Not long before filming began, Colin Clive broke a leg in a horse riding accident. Consequently, most of Henry Frankenstein's scenes were shot with him sitting.