We examined select immunologic parameters in three recipients of a total artificial heart and correlated changes with the clinical course. Two patients remain alive and were studied for 320 and 240 days, respectively; the third died 10 days after implantation. All patients demonstrated transient complement activation immediately postoperatively, as indicated by an increase in plasma levels of C3a des Arg. In the two long-term survivors, C3a des Arg levels again increased, concomitant with intravascular hemolysis associated with high blood shear rates imposed by the drive system of the heart. All three patients had a marked lymphopenia immediately postoperatively, and the two long-term survivors demonstrated marked fluctuations in total lymphocyte count. There was a progressive decline in the number of peripheral blood helper/inducer T cells in the two long-term survivors. A large number of activated (HLA-DR positive) suppressor/cytotoxic T cells were also noted in these two patients. A progressive decrease in B cells was also observed; however, total IgG and IgM levels were not decreased. No changes in neutrophil phagocytic or respiratory burst capacities were identified. The cause of these changes in lymphocyte populations is not clear; however, they may have impact on the use of this device as a bridge to transplantation and may lead to decreased immunocompetence during long-term use.