1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in three models of thrombosis in the rat, and in the tail transection bleeding time test. Heparin was studied as a reference anticoagulant. 2. In the model of venous thrombosis induced by thromboplastin followed by stasis of the abdominal vena cava, argatroban had an ED50 of 125 micrograms kg-1, when administered as an i.v. bolus 5 min prior to the thromboplastin injection: the ED50 of heparin was 42 micrograms kg-1, where ED50 is the dose which reduces the weight of the thrombus by 50% compared with that of the control animals. When the two compounds were administered by continuous i.v. infusion, argatroban (ED50 = 1.5 micrograms kg-1 min-1) had the same potency as heparin (ED50 = 1.2 micrograms kg-1 min-1). 3. Argatroban was active in the arterio-venous shunt model with an ED50 of 0.6 mg kg-1 when the compound was given as a bolus. The ED50 of heparin was 0.04 mg kg-1 under the same conditions. The two compounds had ED50 values of 6 micrograms kg-1 min-1 (argatroban) and 3 micrograms kg-1 min-1 (heparin), when administered by continuous i.v. infusion. 4. When tested against occlusive arterial thrombus formation by electrical stimulation of the left carotid artery, both compounds given as either an i.v. bolus or a continuous infusion led to dose-dependent increases in the duration of post-lesion vessel patency. Heparin bolus was more active than argatroban on a weight basis, in that 2 mg kg-1 gave a similar increase in the time to occlusion as 8 mg kg-1 argatroban. As in the other models, when given as continuous infusions, argatroban (111% increase in time to occlusion at 20 tg kg-1, min-1) had similar activity to that of heparin (180% increase at 25 jg kg-1 min-1) on a weight basis. Hoever, the antithrombotic effects of argatroban were accompanied by only moderate changes in the coagulation parameters (thrombin time and activated partial thromboplastin time, APTT), whereas, even at a subthreshold dose of heparin (12.5 pg kg-1 min-1), both the thrombin time and the APTT were greater than 150 s.5. Infusions of both compounds caused dose-dependent increases in the tail transection bleeding time,with the dose of argatroban that doubles the bleeding time (11 I g kg-1 min-1) being five times greater than that of heparin (EDI, = 2.2 fig kg-1 min-1).6. These data show that, when administered as an intravenous infusion, argatroban is a potent antithrombotic agent in rat models of venous 'mixed' and arterial thrombosis, this effect can be obtained with a lower degree of systemic anticoagulation than with heparin in the arterial model, and argatroban has a lower haemorrhagic potential than that of heparin.