The bactericidal effects of benzoyl peroxide (5% lotion) and hexachlorophene (3% colloidal suspension) against Propionibacterium acnes were compared in nine healthy college students who had the microbiological and skin lipid characteristics typical of acne vulgaris, but no active lesions. Each of the two medications was applied twice daily, to opposite sides of the face, for four consecutive weeks. Hexachlorophene was effective against surface aerobes but only slightly active against P acnes. It marginally reduced free fatty acid concentrations in surface lipids and in follicular porphyrin fluorescence. Conversely, benzoyl peroxide virtually eliminated P acnes and aerobes and induced substantially decreased free fatty acid concentrations and follicular fluorescence. We conclude that benzoyl peroxide exerts its antimicrobial action in the follicles and inhibits P acnes, while the antimicrobial effectiveness of hexachlorophene is limited to the skin surface.