In recent studies in rabbits, high dose aspirin (ASA) which inhibited prostacyclin(PG I2) synthesis by veins augmented thrombus formation in jugular veins. This thrombogenic effect was short-lived and lasted only 1-2 hrs. we have shown that the inhibitory effect of ASA on PG I2 synthesis in arteries lasts much longer than in veins. We therefore examined the effects of high dose ASA on arterial thrombosis in rabbits by measuring PG I2 production, 51cr platelet adhesion and 125I-fibrin accretion onto a mechanically-induced injury site in carotid arteries. PG I2 production, quantitated by a thrombin-induced 14C-5HT release assay, was 0.13 ± 0.01 ng/10 mm2 vessel. 51Cr platelet adhesion and 125 I -fibrin accretion onto these vessels 1 nr after injury was 1.00 ± 0.13 × 106 platelets and 57 ± 5 μg fibrin/10 mm2 respectively (mean = SE, n = 22). After ASA treatment (100 mg/kg, IV), PG I2 production was inhibited by at least 84% for 6 hrs and returned to 56% of control by 20 hrs. This PG I2 inhibition was associated with a marked increase in platelet adhesion (>100%) which lasted for at least 20 hrs. There was no significant increase in fibrin accretion. These results show that the more prolonged effect of ASA on PG I2 production in arteries than in veins is paralleled by a more prolonged thrombogenic effect on arterial vessel wall injury.