The effects of thromboxane (Tx)A2 antagonism were examined in a canine model of platelet-dependent coronary occlusion. The novel TxA2 antagonist (3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbazo lepropanoic acid (Bay u 3405) was studied to ensure that antithrombotic effects seen in vivo were platelet-mediated and did not reflect unspecific compound effects. Bay u 3405 (1, 3, 10 and 30 mg/kg i.v.) inhibited in vivo platelet aggregation and increased the time to thrombotic vascular occlusion by 2.8 h (p less than 0.05) after 30 mg/kg were given. A dose-dependent reduction of intravascular occlusive thrombus growth occurred: thrombus wet weight decreased from 66 +/- 6 mg in vehicle controls to 42 +/- 6 mg, 25 +/- 5 mg, 18 +/- 3 mg and 6 +/- 2 mg after administration of 1, 3, 10 and 30 mg Bay u 3405 i.v., respectively. Electrocardiographic signs for developing myocardial ischemia were largely prevented by the compound. Collagen-induced platelet aggregation ex vivo was inhibited by over 60% in drug-treated animals. The observed delay of thrombotic coronary occlusion reflected an inhibition of platelet aggregation and protection from coronary vasoconstriction at the site of thrombus formation, most likely mediated through blockade of TxA2 receptors.