The relationship between the antithrombotic and anticoagulant effects of heparin was assessed using venous thrombi in rabbits. Accretion of 125I-fibrinogen onto jugular vein thrombi was used to assess the antithrombotic effect of heparin, and the protamine sulfate titration test (heparin activity) and the activated partial thromboplastin time (APTT) were used to measure its anticoagulant effect. The effect of heparin on jugular vein bleeding times was also measured in a separate group of animals. Fibrinogen accretion was significantly lower with continuous infusion than with intermittent injection. Heparin, given by continuous infusion, produced marked inhibition of fibrinogen accretion (to less than 10% of control accretion) at an APTT value of between 75 and 80 sec (control 34 sec) and at a level of heparin activity of 0.4-0.5 U/ml. Infusion of cryoprecipitate reduced the effect of heparin on the APTT relative to its effect on heparin activity. In these cryoprecipitate-treated animals, marked inhibition of fibrinogen accretion occurred at a similar level of heparin activity (0.4-0.6 U/ml) but at a significantly lower APTT (35-50 sec) than in normal animals. On the other hand, there was a progressive increase in jugular vein bleeding time with both increasing APTT values and heparin levels in both groups of animals.