A patient with phenotype R(2)r and anti-C had a hemolytic transfusion reaction (HTR) with hemoglobinemia and hemoglobinuria which occurred within 2 h of receiving an R,r transfusion. Transient impaired renal function ensued. A patient with phenotype R(2)R(2) and anti-Ce+e had the same experience on day 4 after receiving three R(1)r and one rr units. 2 other patients, 1 R(2)r with anti-C who received one R(1)r unit and the other R(2)R(2) with anti- Ce+e who received two R(1)r units, showed no clinical evidence of HTR. Both anti-C antibodies were entirely IgG while both anti-Ce+e antibodies initially were predominantly IgM. IgG subclassing was unsuccessful and red blood cell-mononuclear phagocyte assays were normal. These cases occurred from 1979 to 1981.