C-reactive protein (CRP) is an acute phase reactant which humoral concentration rises drastically following tissue injury or inflammation. CRP of all species binds to phosphorylcholine residues. In the present studies CRP was found to inhibit platelet-activating factor-induced platelet aggregation, and to stabilize platelet membranes against the lytic effect of lysophosphatidylcholine. Inhibition of platelet aggregation by CRP is accompanied by an inhibition of arachidonic acid release from both phosphatidylcholine and phosphatidylinositol. This suggests that phospholipases are inhibited. Hydrolysis of multilamellar dipalmitoylphosphatidylcholine liposomes by purified phospholipase A2, was also inhibited by CRP. These results suggest that CRP can stabilize membranes from the detergent-like effects of lysolipids and from potentially toxic materials such as platelet-activating factor. By inhibition of phospholipases, production of inflammatory mediators would be blocked. CRP might thus act as an early protective recognition mechanism in acute inflammatory states.