Twenty-four patients with multiple myeloma (MM), three (12.5%) in complete remission (CR) and 21 (87.5%) in partial remission (PR) were treated with high-dose chemotherapy (HDCT) (busulfan 12 mg/kg+melphalan 140 mg/m2) as preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation. These cells were previously collected by leukapheresis after mobilization by high-dose cyclophosphamide (HD Cy)+rhGM-CSF (18 patients) or rhG-CSF alone (six patients). Considering 23 evaluable patients following HDCT, the CR rate was 58% (14 patients) and the PR rate was 38% (nine patients). One transplant-related death occurred following this regimen (4%). With a median follow-up of 20 months (range 4-34) after transplantation, 21 patients are alive (87%). Disease progression after transplantation was observed in four patients. Overall and relapse-free actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%) remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis. Busulfan+melphalan is a safe and feasible conditioning regimen for APBSCT in MM with acceptable toxicity and a high objective response rate, which may result in prolonged survival.