Between May 1989 and October 1998, 94 patients with hematological malignancies received allogeneic bone marrow transplantation from HLA-matched related (n = 25), unrelated (n = 16) or 1 locus HLA-mismatched related donors (n = 3). Busulfan (BU) (8mg/kg) and cyclophosphamide (CY) (90mg/kg) with fractionated total boby irradiation (TBI) (12Gy) (n = 30) or BU (16mg/kg) and CY (120mg/kg) (n = 14) were given as conditioning regimen. All patients receiving BU/CY were transplanted from related donors in first remission of acute leukemia or in first chronic phase of CML (standard risk group; S-group). For 30 patients receiving TBI/BU/CY, 13 were transplanted in standard risk and 17 were in advanced stage of hematological malignancies (high risk group; H-group), 7 in S-group and 9 in H-group transplanted from unrelated donor. Severe regimen-related toxicity was found in 10% of patients receiving TBI/BU/CY (one in standard risk group and 2 in high risk group), but not found in patients receiving BU/CY. Probability of disease free survival (DFS) at 5 years was 38% in patients receiving BU/CY, and 43% in patients receiving TBI/BU/CY (52% in S-group and 35% in H-group). For patients transplanted from related donor at standard risk, probability of DFS was higher in patients receiving TBI/BU/CY than in patients receiving BU/CY (83% vs 38%; p<0.05). For patients receiving TBI/BU/CY as preparatory regimen, probability of DFS was higher in patients transplanted from related donors than in patients transplanted from unrelated donors (63% vs 29%; p<0.05), that was due to lower rate of non-relapse mortality (8% vs 61%; p<0.001). Probability of relapse was 33% in patients receiving BU/CY, and 28% in patients receiving TBI/BU/CY (23% in S-group and 31% even in H-group), and no significant difference was found between the three groups. We conclude that this TBI/BU/CY regimen is well tolerated and is very effective in reducing relape and improving survival, especially in standard risk patients transplanted from related donors, and is effective in reducing relapse even in patients transplanted in advanced stage when compared with our historical experience with other conditioning regimen.