The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.