Autoantibodies may cause severe hemolytic anemia, but only rarely are they the cause of a hemolytic transfusion reaction due to the destruction of transfused allogeneic blood. In two patients, autoantibody was detected shortly after blood transfusion. The first case was a D-negative patient who produced an autoanti-Ce and subsequently developed hemoglobinuria and hyperbilirubinemia. The second case was a patient who developed an autoanti-Wrb that caused severe hemolysis that resulted in death.