Clinical application of artificial blood pumps for mechanical circulatory support has been hampered by thromboembolic events. The underlying mechanisms are complicated and may differ from patient to patient. Because the calf is commonly used for artificial heart studies, the object was to determine the value of data gained in an animal model. To this end, the average of 10 calf experiments was compared with three clinical applications of an orthotopically implanted total artificial heart in patients with terminal heart failure. Platelet reactivity was investigated in vitro by collagen-induced whole blood aggregometry, radioimmunoassay methods, and scanning electron microscopy over a 10-day period. An analogous periodicity of platelet function was found in human and animal recipients. Improvement of platelet function preceded that of platelet counts in the early postoperative phase. Exaggerated responses to aggregative agents were observed at days 3 and 7. On the basis of our data, we believe that we can comment about the prospective course of the function and number of human platelets, which may contribute to the identification of critical phases of such treatment, during total artificial heart replacement.