An 11-month-old patient with idiopathic cardiomyopathy was scheduled for orthotopic heart transplantation. A perioperative exchange transfusion was performed because of elevated panel reactive antibody levels. This process was accomplished in the operating room prior to instituting cardiopulmonary bypass using a modified cardiopulmonary bypass circuit. In preparation for the procedure, the cardiopulmonary bypass circuit was primed with washed leukocyte-filtered banked packed red blood cells, fresh-frozen plasma, albumin, and heparin. Pump prime laboratory values were normalized prior to beginning the exchange transfusion. The patient’s blood was downloaded from the venous line just proximal to the venous reservoir while simultaneously transfusing the normalized prime at normothermia. Approximately 125% of the patients calculated blood volume was exchanged. This technique greatly reduces the likelihood of hyperacute rejection. The exchange transfusion process, in addition to the patient immature immune system, provides additional options in orthotopic heart transplantation for patients that may otherwise not be considered suitable candidates.