Seven patients with advanced multiple myeloma, refractory to therapy with alkylating agent-VAD (vincristine-adriamycin-dexamethasone), received a regimen combining high-dose melphalan with total body irradiation supported by autologous bone marrow transplantation. Very rapid, usually greater than 90% tumor mass reduction was achieved in six patients, regardless of prior chemotherapy responsiveness and marrow plasmacytosis up to 30%. Despite signs of early relapse in three patients (median remission duration of all patients, 15 months), five remain alive and well without further cytotoxic therapy from 2 to 21 months (median, 9+ months). Two patients died, one from surgical complications after transplantation and a second due to persistent neutropenia with fatal pneumonia. This treatment provides meaningful disease control for selected patients with resistant myeloma and a poor prognosis.