It has previously been shown that salicylate (S) acts as a vitamin K (vit K)-antagonist inducing a decrease in plasma levels of vit K-dependent clotting factors and inhibiting the vit K-dependent carboxylation reaction in the liver. In this study we evaluated whether this biochemical effect had a possible functional role. Indeed, we tested in rats the antithrombotic potency of S (175 mg/kg/i.p. twice a day for 3 days) on experimentally induced venous thrombosis. Its possible haemorrhagic effect was evaluated by measuring the bleeding time. Low-dose warfarin (W) (0.2, 0.1, 0.1 mg/kg/i.v. for 3 days) was utilized as control drug. To check for a possible potentiation between S and W, we tested the effects of their combination (S + W). Thrombotest was used to monitor the anticoagulant effect of each treatment. The incidence of thrombus formation, after venous stasis, was not significantly affected by any of the treatments used, but a significant reduction in thrombus weight was observed after either S or W treatment. Both drugs partially prolonged the Thrombotest without affecting either the bleeding time or the peri-operative mortality (mainly due to internal bleeding). When the combination S + W was used, no significant benefit was observed on the prevention of thrombus incidence or weight, although a marked Thrombotest prolongation was recorded. On the other hand this combination resulted in a pronounced bleeding tendency, as expressed in a significant prolongation of bleeding time and increased total mortality. Thus S, at doses inducing moderate anticoagulation may prevent venous thrombosis without relevant bleeding complications.