To better define the role of bacteria in inflammatory acne vulgaris, we have investigated the ability of four strains of Propionibacterium acnes and three strains of Propionibacterium granulosum to activate complement. Complement activation was assayed by incubating normal human serum with varying concentrations of each strain and measuring residual total hemolytic complement activity. When serum was tested unaltered, P. acnes strains were approximately threefold more potent than an equal weight of P. granulosum in consuming complement, which could reflect classical and/or alternative pathway activation. All strains also consumed complement in serum chelated with ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid, which selectively assays alternative pathway activation. Incubation of unaltered serum with both P. acnes and P. granulosum resulted in immunoelectrophoretic conversion of C4, C3, and factor B of the alternative pathway. Incubation of chelated serum resulted in conversion of C3 and factor B. These data taken together suggest that both species can activate complement through either pathway. Serum incubated with P. acnes was chemotactic for polymorphonuclear leukocytes, and this chemotactic activity was largely C5 dependent as shown by antibody inhibition. It is suggested that complement activation may occur in vivo in acne, and the inflammatory response may be contributed to by the generation of C5-dependent chemotactic factors.