Forty-four out of 258 allogeneic BMT were performed across the major ABO barrier. Donor erythrocyte repopulation could be evaluated in 30 cases. Fifty-eight patients transplanted with an ABO compatible or minor incompatible graft served as the control group. All patients received a marrow graft depleted of lymphocytes by counterflow centrifugation. Less than 10(8) residual erythrocytes were present in the graft. Cyclosporin A was used as immunoprophylaxis after transplantation. Erythrocyte repopulation was measured using a fluorescent microsphere method. An adapted transfusion policy was applied. Eight out of 30 patients (27%) with major ABO incompatibility had no detectable donor erythrocytes 2 months after BMT. Up to 3 months after BMT donor erythrocyte repopulation was significantly delayed in the ABO incompatible group (P < or = 0.03). Significantly more erythrocyte transfusions were required in the ABO incompatible group (P < 0.001). Six patients with blood group O (20%) developed pure red cell aplasia which resolved in five without therapeutic intervention. In these six patients anti-A antibody titers were persistently high the first 3 months after BMT. This was in contrast with 22 patients with timely recovery of erythropoiesis in whom anti-A and anti-B antibody titers showed a steady decrease after BMT. The incidence of immunohematological complications in these patients who received a lymphocyte depleted major ABO incompatible graft is similar (20%) to the incidence reported in the literature. Serious morbidity related to major ABO incompatibility did not occur.