Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.