We report the inactivation of the third component of complement (C3) In this study, we treated C3 with primary amines and compared the rate of decay of C3 hemolytic activity with the rate of loss of surface-binding activity. We find both rates to be identical, indicating that both activities are causally related. We also present data to support our hypothesis (7) that there is an internal ester bond within C3 and that C3b binds to RS by the transfer of the acyl group of the internal ester to a hydroxyl group on the RS. C4 and C5 were also treated with hydroxylamine and methylamine. C4, which binds covalently to membrane surfaces (8), behaves like C3 in these experiments. C5, which does not bind covalently to cell surfaces (8), is not inactivated by hydroxylamine and methylamine.