The potential antithrombotic action of losartan, the AT1 receptor antagonist, in an experimental model of venous thrombosis in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) was tested. The involvement of nitric oxide and prostacyclin in this effect was also studied. Venous stasis was induced by ligation of the vena cava. Losartan, after administration of a single, hypotensive dose (10 mg/kg, p.o.), significantly reduced the thrombus weight in SHR but not in WKY. The antithrombotic activity of losartan in SHR was abolished by NG-nitro L-arginine methyl ester (L-NAME) (30 mg/kg s.c.) but not by indomethacin (2.5 mg/kg s.c.). No changes in primary hemostasis, platelet aggregation, coagulation parameters such as activated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, and fibrinogen level, either in SHR or in WKY rats, were found. Our results indicate the NO-dependent mechanism in the antithrombotic effect of losartan on venous thrombosis in SHR.