The subunit composition of human C3 and C5 was analyzed. Acrylamide gel electrophoresis of the fully reduced and dissociated proteins disclosed a similar structure, consisting of one alpha and beta subunit, linked together by one or more disulfide bonds. The approximate molecular weights for the alpha and beta subunits of C3 as well as C5 were 140,000 and 80,000 respectively. C42 caused cleavage solely of C3alpha, whereas trypsin affected both C3alpha as well as C3beta. A characteristic subunit modification by both enzmes indicated that C3alpha constitutes the source of C3a. C423 as well as trypsin exclusively affect C5alpha. C5a therefore appears to originate from the C5alpha subunit. The mode of primary cleavage by C423 and trypsin differs, giving rise to different forms of C5b. The questions is raised if multiple forms of C5a also exist. It appeared from our studies that certain forms of C5b may retain portions of the alpha subunit, which could potentially release some biologically active split products following secondary cleavage by the appropriate enzyme.