Interferon-alpha-2b has been demonstrated to prolong remission duration and survival in responding multiple myeloma patients. The aim of this study was to evaluate intensification of this maintenance therapy through the addition of glucocorticoids. Eighteen myeloma patients at diagnosis received six-12 courses of conventional chemotherapy and then interferon + glucocorticoids. This treatment included 3 megaunits of interferon three times a week, plus 4 days of pulsed high-dose dexamethasone (40 mg/d for 4 d every 28 d for 6 months/year) in patients < 70 yr old, or oral prednisone (50 mg three times a wk) in patients > 70 yr old. Conventional chemotherapy induced an objective response in 13/18 patients and a further reduction of the M component (> 50%) was achieved during interferon + glucocorticoids treatment in 7/13. 4/18 patients relapsed with a median follow-up of 22 months (range 13-40). These findings indicate that interferon + glucocorticoids, after inductional chemotherapy, further reduces tumor burden and may prolong remission.