The degree of red cell destruction in human recipients of the total artificial heart has not previously been described. Fifteen patients implanted with a Jarvik-7 total artificial heart for either temporary or permanent heart replacement were reviewed. Clinically significant elevations of plasma free hemoglobin and serum lactate dehydrogenase were demonstrated in patients receiving the standard (100 ml) Jarvik-7 containing Medtronic-Hall valves and powered by pulses of compressed air delivered at a dP/dT of 6000 mm Hg/sec to 8000 mm Hg/sec. Reduction of the dP/dT by drive unit modification greatly reduced the plasma free hemoglobin and lactate dehydrogenase in subsequent patients. Introduction of the smaller (70 ml) total artificial heart was not associated with greater hemolysis once dP/dT had been reduced. With the current driver delivering systolic pulses at less than 4500 mm Hg/sec, both size hearts are free of clinically relevant hemolysis. In addition, it appears that attempts to eliminate hemolysis completely by lowering heart rates, cardiac outputs, or driving pressures are potentially dangerous. The eventual development of embolic cerebrovascular accidents is associated statistically with heart rates below 80 beats/min. These data reassure implanting physicians that the updated Jarvik-7 total artificial heart system does not induce worrisome hemolysis. In addition, this study has uncovered a link between eventual cerebrovascular accident and low heart rate, implying that purposeful application of heart rates around 100 beats/min may provide a significant margin of protection against cerebrovascular accident during implantation.