A clinical survey of 4895 heart transplants performed at 66 centers worldwide revealed that eight patients (0.16%) had received ABO-incompatible donor hearts. Of these eight transplants, five hearts (63%) were hyperacutely rejected (vascular or humoral rejection), four within 24 hours and one (after treatment by plasmapheresis) at 13 days. Two patients died at the time of rejection; the remaining three underwent retransplantation. Two patients died (at retransplant and at 7 weeks, respectively), and one is alive 8 months later. Three ABO-incompatible hearts (37%) were not hyperacutely rejected; two of these patients remain alive 12 and 26 months later, and the third died at 11 months in an automobile accident. There was, therefore, an early mortality of four of eight patients (50%). Care should be taken to ensure ABO compatibility of the donor whenever heart transplantation is undertaken.