The antithrombotic activities of aspirin, the thromboxane (Tx) A2/prostaglandin endoperoxide-receptor (TP-receptor) antagonist, SQ 30,741, and heparin were determined in anesthetized rats. Heparin (3 doses of 50, 300 U/kg), aspirin (1 and 10 mg/kg), SQ 30,741 (1 mg/kg + 1 mg/kg/h), or the combination of SQ 30,741 and aspirin (10 mg/kg) was administered intravenously before inducing occlusive thrombosis with 0.1-mA stimulation of the intimal surface of the carotid artery. Light and electron microscopy revealed the thrombi to be composed predominantly of platelets enmeshed in a fibrin network. Heparin (300 U/kg), SQ 30,741 and SQ 30,741 + aspirin decreased average thrombus weight by 54, 57 and 39%, respectively. These treatments also reduced the incidence of occlusion and improved carotid blood flow during thrombosis. In contrast, aspirin alone (1 and 10 mg/kg) and the lower heparin dose (50 U/kg) did not significantly affect thrombus weight or carotid blood flow. To verify adequate drug dosage, pharmacological activities were characterized ex vivo in separate rats. Aspirin (10 mg/kg) inhibited maximum thromboxane (Tx) B2 production in whole blood by 99 +/- 1% and SQ 30,741 blocked 96% of platelet TP-receptors. Heparin increased the activated partial thromboplastin time (APTT) partially at 50 U/kg (approximately 3-fold) and maximally at 300 U/kg (> 10-fold). These experiments demonstrate the contribution of platelet and coagulation mechanisms to a thrombosis model which is sensitive to a TP-receptor antagonist, but not aspirin.