Twelve of 58 (21%) evaluable patients of blood group 0 who received a bone marrow transplant (BMT) from an HLA-matched sibling of a donor of group A or B developed significant immunohematologic problems in the posttransplant period. Anti-A or anti-B isohemagglutinins persisted for longer than 120 days post-BMT in nine patients and are still present in three patients at days +162 to +605. Red cell production as indicated by a reticulocyte count of greater than 0.5% was delayed to 40 days or more in nine patients, and in five of these was markedly delayed to 170 days or longer. One patient does not as yet have red cell production on day +605 in spite of having had 13 plasma exchanges performed to reduce the anti-B titer. Five patients experienced overt hemolysis, manifested by a sudden drop in hemoglobin of 1.5 to 4 gm/dl (median = 2.5 mg/dl), starting on day +37 to +105 (median = +65), persisting for 10 to 94 days (median = 36 days). Hemolysis and a delay in the onset of erythropoiesis beyond 170 days were more frequent in 30 patients treated with cyclosporine/prednisone than in 28 patients treated with methotrexate/prednisone for graft-versus-host disease prophylaxis. Our data indicate that ABO major mismatched BMT can be associated with significant immunohematologic consequences, some of which occur more frequently in association with cyclosporine administration.