In the pediatric age group shortage of donor hearts leads to mortality rates of 30-50% on the waiting list. Because of the immaturity of the immune system of infants, ABO-incompatible heart transplantation may be an option to increase donor availability. We transplanted two infants with blood type O at the age of 7 and 5 months, respectively, with complex congenital heart disease. Intraoperative plasma exchange was performed during cardiopulmonary bypass followed by standard immunosuppression. Both recipients received a blood type A donor organ. Plasma was exchanged up to six times until anti-A antibodies were eliminated. No hyperacute rejection occurred, ventricular function is excellent and there have been no acute rejection episodes up to 4 months after transplantation. Anti-A antibody titers remained low and eventually disappeared. ABO-incompatible cardiac transplantation shows good short-term results in young infants and appears to be a safe procedure to reduce mortality on the waiting list.