Bone marrow transplantation (BMT) in the presence of major ABO incompatibility presents the risk of a potentially fatal hemolytic transfusion reaction at the time of marrow infusion. We describe the use of a forced alkaline hydration/mannitol diuresis regimen in combination with red blood cell (RBC) reduced bone marrow given as buffy coat in 5 patients undergoing allogeneic BMT from ABO incompatible donors. Three patients had ABO antibody titers of 1:32 and were not subjected to antibody removal procedures. Two patients with respective antibody titers of 1:512 and 1:128 underwent plasmapheresis to reduce the antibody titers to below 1:64. The forced diuresis/mannitol regimen was well tolerated. Although the RBC content was still high in the buffy coat preparation a significant hemolytic transfusion reaction was successfully prevented. No patient had back pain, hyperbilirubinemia or renal impairment despite clinical and laboratory evidence of hemoglobinuria. These data indicate that patients with antibody titers below 1:64 might be spared the risks and cost associated with plasmapheresis or complete RBC depletion of the bone marrow transplant.