Low dose heparin therapy has been used routinely for prophylaxis of deep venous thrombosis, yet in vitro data regarding its antithrombotic effects are sparse. The effects of heparin on venous thrombus formation were studied in an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying heparin doses and perfused at a shear rate of 100 sec-1 over everted, injured porcine vein segments, simulating conditions in the venous circulation. Platelet and fibrin deposition were measured by use of indium 111 and iodine 125 radiolabels, respectively. The effects of heparin on the intrinsic coagulation cascade were monitored by the activated clotting time. Increasing doses of heparin resulted in significant reductions in fibrin and platelet deposition (ANOVA F = 2.67 and 3.17, respectively, p less than 0.05). At a dose of only 0.19 USP units/ml blood, equivalent to a 1000 unit bolus of heparin in a 70 kg man, a noticeable reduction in both fibrin and platelet deposition was observed without an increase in the activated clotting time. These data confirm the antithrombotic effects of heparin at low dose ranges and may explain the clinically observed phenomenon of deep venous prophylaxis without an appreciable alteration in the conventional coagulation assays.