The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent:batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.