An immunofluorescence investigation of thirty-six non-inflamed and thirty-four inflamed acne lesions has been carried out. Fluorescence for C3, unaccompanied by fluorescence for immunoglobulins, was found in the walls of dermal blood vessels or at the basement membrane zone of the comedo or at both these sites in fifty-seven lesions. Fluorescence for C3 accompanied by fluorescence for immunoglobulins was found in nine lesions. In two papules and three nodules the comedo was surrounded or replaced by a mononuclear cell infiltrate. These findings have been taken to indicate that cellular immune mechanisms are a late event and activation of complement is an early event in the pathogenesis of inflammation in acne. The mechanism of complement activation remains uncertain.