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The Spiral Staircase is based on Some Must Watch, a novel by English crime writer Ethel Lina White (1876-1944). The novel was adapted for the movie by screenwriter Mel Dinelli. It was remade in 1975 as The Spiral Staircase (1975).

The novel was set in Wales. The movie changed the setting to Massachusetts.

The entire movie was filmed on a soundstage using the sets from another movie, Orson Welles' The Magnificent Ambersons (1942). The spiral staircase was also used in Val Lewton's Cat People (1942), which, incidentally, also featured Kent Smith in a starring role.

Helen (Dorothy McGuire) had "hysterical muteness," caused by the shock of seeing her parents burned to death in a fire that also destroyed their home. She was spared because she was just returning home from school at the time.

Helen finds that Blanche (Rhonda Fleming) has been murdered and, suspecting that Steve (Gordon Oliver) is the killer, she locks him in the basement and tries to call Dr Parry (Kent Smith) but cannot say the words. Professor Warren helps her upstairs. On the way, he reveals himself as the killer of women who have imperfections. Helen manages to get away from him and lock herself into Mrs Warren's (Ethel Barrymore) bedroom, where she searches for the gun but to no avail. She races through the house, trying to alert the constable outside, but he drives away in the storm. She descends the staircase but sees a shadow at the bottom and runs back up. Professor Warren goes after her but, halfway up the stairs, he is shot by Mrs Warren, who apparently has found the gun. Helen releases Steve from the basement. Mrs Warren collapses on the stairs and apologizes to Steve for believing that he was the killer because Warren always waited to do his killings when Steve came home. In the final scene, Helen telephones Dr Parry and speaks for the first time. She then sinks to the floor and sobs.

She quietly whispers, "No", after Mrs Warren collapses on the staircase. She then phones Dr Parry and gives the operator his telephone number "1...8...9...", and adds, "Dr Parry, come. It's Helen."