Complement cleavage product C3b was examined for its effect on macrophages. Albumin-elicited guinea pig peritoneal macrophages kept in short-term culture were challenged with purified homologous C3b, and release of oxygen and arachidonic acid metabolites was studied. C3b at concentrations ranging from 20 to 80 micrograms/ml induced synthesis of large quantities of the arachidonic acid cyclooxygenation products thromboxane B2 (TXB2) and prostaglandin E (PGE) but failed to trigger an oxidative burst. Our findings link together macrophages, complement, and arachidonate metabolites as major participants in inflammatory responses.