Fifteen patients with stage II-III multiple myeloma were intended to undergo two sequential cycles of myeloablative chemoradiotherapy with autologous bone marrow or blood stem cell transplantation after response to primary induction chemotherapy. BM grafts were used in 13 of the 15 first transplants whereas PBSC were used for the two remaining first transplants and all second transplants. The preparative regimen was melphalan 200 mg/m2 for the first transplant and melphalan 140 mg/m2 plus total body irradiation (TBI) 10 Gy for the second. Before the first transplant, 12 patients were in PR and three in CR whereas seven were in CR and seven in PR after the first transplantation. Four patients received only one cycle of myeloablative therapy because of incomplete hematopoietic reconstitution after transplantation (three patients) and early death (one patient). Eleven patients proceeded to the second transplant, and six patients were then in CR and five in PR. After the second transplant a further two patients entered CR whereas three remained in PR. Of all 15 patients, 11 remain in continuous complete (eight patients) or partial (3 patients) remission at a mean time of 20 months after the first transplant. Five patients in CR were examined by PCR analysis of the clone-specific immunoglobulin gene rearrangement for detection of minimal residual disease and four of these are PCR-negative up to 33 months after the first transplant. One transplant-related death occurred, and one patient died from progressive disease. This superintensive treatment regimen for younger patients with multiple myeloma has acceptable toxicity, and can induce and sustain long-term complete remissions.