Recipients of the total artificial heart are at risk for device-related thrombus formation and thromboembolism. Platelet and fibrin metabolism was studied in four patients who received the Jarvik 7 total artificial heart as a bridge to transplantation and in eight patients after orthotopic heart transplantation. Platelet activation was assessed by measurement of plasma levels of beta-thromboglobulin, fibrin formation by fibrinopeptide A, and fibrinolysis by cross-linked fibrin degradation products. These markers were increased after surgery with only minimal differences between the two patient groups for the first 3 days. In comparison to heart transplant patients, these markers remained elevated in artificial heart recipients despite anticoagulation therapy. beta-Thromboglobulin levels did not decrease in two artificial heart recipients who received aspirin. Markers of platelet and fibrin activity were greatly increased in one artificial heart recipient who had impaired inflow into the device, was not anticoagulated because of bleeding, and had extensive device-related thrombus on explantation. Plasma markers of platelet and fibrin metabolism provide biochemical assessment of in vivo thrombus activity in artificial heart recipients. Monitoring these markers may provide an additional means of guiding anticoagulation therapy in patients with artificial hearts and assessing interventions designed to reduce device-related thrombus formation.