Summary:Delayed erythropoiesis and pure red cell aplasia (PRCA) have been reported after major ABO-incompatible BMT. We attempted to find risk factors for the development of PRCA in 27 patients who underwent major ABO-incompatible BMT. In all patients, the donor marrow was depleted of RBCs before infusion. In 22 patients, isoagglutinins were determined until they disappeared. In eight (29.6%) out of 27 patients, bone marrow examination following BMT showed the findings of PRCA. We analyzed various clinico-pathologic risk factors and isoagglutinin type was the only significant risk factor. Patients with anti-A isoagglutinins against donor RBC developed PRCA more frequently than patients with anti-B (8/17 vs 0/9). Median days to the disappearance of isoagglutinins tended to be longer in patients with PRCA (PRCA vs non-PRCA, 200 vs 66 days) and in cases with anti-A isoagglutinins (anti-A vs anti-B, 160 vs 51 days). Times to disappearance of isoagglutinins correlated with times to reticulocytes over 1% and initial appearance of donor type RBC (R 2 = 0.708 and 0.711). In conclusion, RBC engraftment following major ABO-incompatible BMT was dependent on the disappearance of isoagglutinins against donor RBC, and anti-A isoagglutinin was a risk factor for the development of PRCA after major ABO-incompatible allogeneic BMT. Bone Marrow Transplantation (2000) 25, 179-184. Keywords: anti-A isoagglutinin; PRCA; ABO-incompatible BMT Major donor-recipient ABO incompatibility is not considered to be a contraindication to successful bone marrow transplantation (BMT). Acute hemolysis by anti-A or anti-B isoagglutinins of recipient origin at the time of donor marrow infusion can effectively be prevented by the removal of anti-A or anti-B isoagglutinins from the recipients or by the depletion of red blood cells from marrow grafts. [1][2][3][4] Previous studies showed no significant effect of major ABO mismatch on the incidence of graft rejection, the incidence of graft-