The individual and combined effects of PGD2, PGI2 and an aortic proteoglycan on human platelet aggregation and plasma clotting were studied. PGI2 was at least 10 times more potent than PGD2 in inhibiting platelet aggregation. Small doses of prostaglandins inhibited ADP- and thrombin-induced aggregation, but only prolonged aggregation time without affecting the extent of arachidonic acid (AA)-induced aggregation. Small doses of prostaglandins did not affect thrombin-induced clotting of PRP. Large doses of prostaglandins abolished platelet aggregation and prolonged the onset of thrombin-induced clotting. The aortic proteoglycan (APG) had no appreciable effect on ADP- or AA-induced aggregation. Small doses of APG abolished thrombin-induced clotting, while large doses of APG suppressed both clotting and aggregation induced by thrombin. PGI2 and PGD2 showed additive inhibition of platelet aggregation regardless how the aggregation was induced. APG and prostaglandins showed additive inhibition of only thrombin-induced aggregation. APG, but not any of the prostaglandins, prolonged clotting time of PPP. This prolongation was not potentiated by PGI2 or PGD2.