Among 2752 patients with acute leukemia who had recurrent leukemia after autograft in remission and were reported to the EBMT, 94 underwent an allogeneic bone marrow transplant and 74 received a second autograft. Recipients of HLA-mismatched related or unrelated bone marrow had an increased transplant-related mortality (TRM, P = 0.017) and a decreased leukemia-free survival (LFS, P = 0.03), compared to recipients of HLA matched related or unrelated bone marrow. Outcome in recipients of HLA-compatible related or unrelated bone marrow was compared to those receiving a second autograft. TRM at 2 years was 51 +/- 8% in recipients of matched allografts and 26 +/- 6% following a 2nd autograft (P < 0.05). Two-year LFS was 27 +/- 7% and 35 +/- 6% in the two groups, respectively (NS). Multivariate analysis in these two groups showed that TRM was increased in patients who were in 2nd or later remission at 1st autograft (P < 0. 05) and allograft recipients (P < 0.05). Relapse was more common in patients with ALL (P < 0.001), above 25 years of age (P < 0.02), autograft performed later than 1991 (P < 0.05), and in second autografts (P < 0.05). LFS was decreased in patients >25 years of age (P < 0.01), if the interval from first autograft to relapse was 8 months or less (P < 0.01) and if TBI was used at first autograft (P < 0.05).