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A stage actor, Melford began appearing in films in 1909 and was directing by the early teens. Notable among his silent films are the Rudolph Valentino vehicles The Sheik and Moran of the Lady Letty; the standout among his talkies is the Spanish-language version of Dracula, which he shot on the sets of Tod Browning's 1931 film. In the late '30s Melford left directing and returned to acting, and appeared in several major films of the '40s, including the comedy My Little Chickadee with W.C. Fields and Mae West; Preston Sturges' classic farces The Miracle of Morgan's Creek and Hail the Conquering Hero; and Elia Kazan's debut feature A Tree Grows in Brookly.