The development of iso- and alloantibodies reactive with recipient red blood cells subsequent to organ transplantation is an established phenomenon. However, development of self-reactive antibodies in multiple recipients of organs from a single donor source has only been reported in one instance involving the formation of anti-D after transplantation. We observed the development of a delayed hemolytic transfusion reaction 10 days after transplantation of a group O liver into a group A recipient. Serologic studies revealed a positive direct antiglobulin test due to coating of autologous A cells with anti-A. Close follow-up of the group A recipients of the kidneys transplanted from the same group O donor revealed development of hemolysis secondary to anti-A on day 11 in one recipient and hemolysis due to anti-A on day 13 in a second recipient. Significant anemia, a 2-3 g/dl drop in hemoglobin, occurred in both kidney recipients. These findings suggest that recipient of organs from donors whose transferred lymphocytes have produced antirecipient RBC antibodies in another recipient may be at risk for developing a similar self-limited hemolytic episode and should be followed accordingly.