In 1988, a prospective, randomized multicenter study was initiated to determine the efficacy of a combined induction regimen with recombinant interferon-alpha-2b (IFN-alpha) and maintenance with IFN-alpha on the response and survival rates in multiple myeloma (MM) patients. Induction therapy consisted of VMCP (vincristine, melphalan, cyclophosphamide, prednisone), randomized to combine IFN-alpha at a dose of 2 x 10(6) U, 5 days per week throughout the induction period of 12 months. Patients who achieved plateau phase were subsequently randomized again between IFN alpha maintenance (2 x 10(6) U, 3 days a week) for 12 months and no maintenance therapy. Of the previously untreated patients, 84 were initially randomized for induction therapy, and 31 for the maintenance phase with IFN-alpha. Results of the cohort median survival, based on the intention to treat, have shown that those on the VMCP/IFN-alpha arm had a median survival of 53 months, compared with patients on the VMCP induction arm who a median survival of 26 months (P = 0.052). The median survival of stage 3 evaluable patients who were on the VMCP/IFN induction arm was 43 months, and 13 months for patients treated by VMCP alone (P = 0.008). No significant difference in survival was detected among patients in partial remission (after induction) who had a second IFN-alpha randomization at the plateau phase. Hematologic toxicity, mild to moderate fever, and fatigue were more common in the VMCP/IFN induction arm. The results show that VMCP/IFN is a well-tolerated treatment regimen, and is superior to VMCP for patients with stage 3 myeloma.