We have investigated the effects of R68070 on platelet function in vitro and in vivo. The drug inhibits U46619-induced aggregation (IC50 = 1.2 x 10(-6) mol/L), blocks serum thromboxane formation (IC50 = 1 x 10(- 7) mol/L), and increases serum prostaglandin (PG)E2 and 6-keto-PGF1 alpha levels, indicating that it combines thromboxane receptor blocking and thromboxane synthase inhibiting properties. The thromboxane- dependent aggregation of blood platelets is blocked by R68070, whereas no inhibition of thromboxane independent pathways occurs. A double- blind, randomized, cross-over study was performed on nine volunteers, comparing 400 mg placebo, 400 mg aspirin, and 400 mg R68070. Thromboxane-dependent aggregations were significantly inhibited by R68070 and by aspirin, the latter still having the most pronounced action. However, R68070 was clearly more powerful than aspirin (P less than .0005) in prolonging the bleeding time. Serum TxB2 formation was completely inhibited with both treatments, whereas serum 6-keto-PGF1 alpha and PGE2 and intralesional 6-keto-PGF1 alpha were inhibited after aspirin and stimulated after R68070. We conclude that R68070 inhibits platelet thromboxane synthase and its thromboxane receptor both in vitro and in vivo; local reorientation of cyclic endoperoxide metabolism toward prostacyclin induces a stronger inhibition of hemostasis than that produced by aspirin.