More than 25 years of experience performing heart surgery on Jehovah's Witnesses has culminated in successful cardiac transplantation without administering blood products in five patients (mean age, 44.4 +/- 8.3 years) of this faith. The use of blood-conserving methods, iron supplementation, bone marrow-sparing maintenance immunotherapy, and brisk postoperative diuresis has added to the efficacy of cardiac transplantation in these patients. No perioperative deaths occurred, and early follow-up studies have shown that these patients have not been more susceptible to higher graft rejection rates due to the lack of pretransplant blood transfusions. As more Jehovah's Witnesses undergo heart transplantation in the future, comparison with other recipients who allow pretransplant blood transfusions may lead to a better understanding of rejection immunobiology. We conclude that cardiac transplants may be safely offered to Jehovah's Witnesses without fear of a uniformly poor outcome.