We report that cloricromene (5-30 microM) inhibited thrombin-induced platelet aggregation and synergized with other antiplatelet compounds. The antiaggregatory effect of subthreshold concentrations of the prostaglandin (PG)I2 analogue, iloprost (0.2 nM), or of sodium nitroprusside (1 micron), acting through a nitric oxide (NO)-like mechanism, was significantly potentiated by co-incubation with cloricromene (5 microM). In addition, cloricromene enhanced the antiplatelet activity of the NO-like factor released by peritoneal rat polymorphonuclear cells. Thus, the present results show that cloricromene possesses direct antiplatelet properties and synergizes with other endogenous as well as exogenous antiplatelet compounds.