Thromboembolism is a serious complication of prolonged use of intracirculatory devices such as total artificial hearts (TAH) and ventricular assist devices. The authors have evaluated alteration in the hemostatic system associated with long-term use of TAH and ventricular assist devices. This article reports results of a prospective evaluation of the fibrinolytic system in four calves implanted with TAHs and four with ventricular assist devices. Blood fibrinolytic activity measured with a solid phase radiometric assay was elevated in two of four TAH calves; plasma plasminogen activity was increased in three. Plasma plasminogen activator activity was undetectable (normal) in all animals. Slight to moderate hypofibrinogenemia was noted in all TAH calves. Calves implanted with a left ventricular assist device had mostly normal blood fibrinolytic activity, fibrinogen, and plasminogen levels. Fibrinogen survival was measured in two calves with ventricular assist devices and three with TAH and was in the normal range in all of these animals. No significant thrombotic lesions were noted at autopsy in five calves that died or were electively killed. These observations suggest enhanced activation of the fibrinolytic system in some calves implanted with a TAH. This may offer a measure of protection against thrombosis in some animals.