The role of the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptor and the efficacy of GPIIb/IIIa receptor antagonists on reocclusion after arterial versus venous thrombolysis is unknown. We used a canine model of simultaneous carotid artery and jugular vein thrombosis to evaluate the effect of the murine monoclonal antibody 7E3 [7E3 F(ab')2] on intravascular thrombotic reocclusion after thrombolysis in both vessels. The left carotid artery and right jugular vein were instrumented with flow probes, a critical stenosis, and an electrode through which an anodal current was applied to induce formation of an occlusive thrombus. After persistent occlusion of both vessels, 7E3 (0.8 mg/kg, n = 7) or saline (n = 10) was administered intravenously (i.v.) immediately after the local administration of anisolylated plasminogen streptokinase activator complex (APSAC, 0.1 U/kg). Ex vivo platelet aggregation in response to ADP or arachidonic acid was inhibited completely, and bleeding time was increased threefold by 7E3. The administration of 7E3 did not affect the activated partial thromboplastin time as compared with control values. The time to reperfusion of either vessel was not altered significantly in the presence of 7E3. Arterial or venous thrombolysis after APSAC was achieved in 10 of 10 and 8 of 10 control animals, respectively, but rethrombosis occurred in both the carotid artery and jugular vein in each of the saline-treated animals. Treatment with 7E3 prevented cyclic flow variations and reocclusion in the carotid artery (p < 0.05) in all treated animals (n = 7). In contrast, 7E3 did not suppress cyclic flow variations in the jugular vein, and rethrombosis occurred in five of six vessels despite the presence of platelet inhibition as assessed ex vivo. Residual arterial thrombus weights were reduced by pretreatment with 7E3 (saline = 24 +/- 4 mg, 7E3 = 11 +/- 3 mg; p < 0.05), whereas residual venous thrombus weights were not affected (saline 25 +/- 5 mg and 7E3 26 +/- 11 mg). The results indicate that inhibition of the platelet GPIIb/IIIa receptor does not prevent jugular vein rethrombosis despite its ability to prevent rethrombosis in the carotid artery. Different thrombotic mechanisms are involved in forming arterial and venous thrombi. Interventions that modulate arterial thrombotic events need not affect occlusive thrombotic activity in the venous circulation.