Severe aplastic anemia (sAA) is a bone marrow failure disorder which is mostly a consequence of immunologically mediated stem cell destruction. Allogeneic bone marrow transplantation (BMT) from a compatible donor provides long-term survival in 60 to 80% of sAA patients. However, graft rejection still remains a major problem, and a second allograft is an alternative for these patients. We retrospectively analyzed 34 patients who received a second BMT (BMT2), nine with primary graft failure (PGF) and 25 with transient engraftment (TE). The probability of survival at 13 years among PGF patients was 22% vs 60% for the TE group (P = 0.0068). Age (<17 vs>17 years), number of mononuclear cells (<3 vs >3 x 10(8)/kg) and year of transplant (1986-1991 vs 1992-1998) at BMT2 had no statistical influence on survival. A significant survival advantage was noted among TE patients (P = 0.0068), which was probably because of a longer intertransplant interval (>90 days). Furthermore, 90% of patients with positive blood cultures at BMT2 did not survive the procedure. We conclude that early detection of primary graft failure (PGF), followed by measures attempting to promote hematopoietic recovery (eg use of growth factors, further infusion of stem cells) may decrease mortality.