Incubation of normal human serum with 3-5 mM Mergetpa causes activation of the alternative pathway of complement as indicated by fragmentation of C3 and factor B, dependent on the presence of divalent cations. Mergetpa inhibits the regulatory protein factor I and, as a consequence, may allow initiation of the feedback cycle of the alternative pathway by deregulation. The classical pathway is not or only to a minor extent activated. A decrease in the hemolytic activity of C2, C5 and one or several of the components C6-9 in the presence of 5 mM Mergetpa may be explained by direct inactivation. The described effects are probably mediated by Mergetpa acting as a thiol.