Busulfan and cyclophosphamide (BuCy) are currently the most widely used myeloablative regimen to treat malignancies with allogeneic stem cell transplantation. Fludarabine has considerable efficacy in both immunosuppression and tumor cells killing with a minimal extramedullary toxicity. We evaluated the efficacy of 40 mg/m(2) fludarabine i.v. for 5 days and busulfan 4 mg/kg/day p.o. for 4 days as myeloablative conditioning regimen in 70 patients (median age 24 years) with acute leukemia or chronic phase of myelogenous leukemia. They all had human leukocyte antigen-matched sibling donors. The patients received 10 mug/kg granulocyte colony stimulating factor (GCSF), 24 h after stem cell infusion until engraftment occurred. Graft-versus-host disease (GVHD) prophylaxis included 3 mg/kg cyclosporine-A i.v. from day -2 to +6 followed by 12 mg/kg p.o. until day +60. The median time of neutrophil recovery (>0.5 x 109/l) and platelet recovery (>20 x 109/l) were 10 and 12 days, respectively. Mucositis (93%) and hepatic toxicity (16%) resolved with conservative therapy. The incidence of acute GVHD grade I-II and III-IV were 38.6 and 15.7% respectively. Overall survival and disease-free survival were 71 and 64% respectively with 17 months median follow-up for surviving patients. We conclude that FluBu may be used as a substitute for BuCy with almost the same efficacy and with a lower transplant adverse effect but to increase anti-leukemic effects, especially in acute lymphoblastic leukemia patients, it needs some modifications.