Six patients (aged 39 to 55 years) with stage III myelomas were treated with IV high dose melphalan (HDM) 140 mg/m2. They had previously received only one or two courses of conventional chemotherapy. The extrahematological tolerance of the procedure was good. The duration of neutropenias (less than 500/mm3) was 14 to 24 days. Complete remission (CR) was obtained in 4 cases but one patient died in CR of invasive aspergillosis. In the other 3 cases, bone marrow was cryopreserved without ex vivo treatment and reinfused after a 2nd course of HDM. These patients remain in apparent CR 12, 20 and 34 months after the diagnosis although one of them had a pure meningeal relapse treated with a second autograft. These results suggest that CR can be obtained with HDM but at the expense of profound myelosuppression. Long term disease control can be obtained but the role of the 2nd course of HDM with autologous bone marrow transplantation warrants further study.