Interferon-alpha-2b (IFN) has been demonstrated to prolong remission duration and survival in responding multiple myeloma (MM) patients. The aim of this study was to intensity maintenance therapy adding glucocorticoids (GLU) to the standard IFN therapy. Twenty-eight relapsed MMs with stable disease or response after conventional chemotherapy received IFN+GLU. The treatment included 3 megaunits of IFN 3 times a week continuously until relapse, plus 4 days pulsed high-dose dexamethasone (40 mg/day for 4 days every 28 days for 6 consecutive months every 12 months) in patients < 70 years, or oral prednisone (PDN, 50 mg 3 times a week) in patients > 70 years, both until relapse. Conventional chemotherapy induced a response in 12/28 MMs. For all patients the actuarial median progression-free survival from relapse was 24 months and the survival from relapse 42 months with no difference between responding and nonresponding patients. The first duration of tumor control, i.e. the interval from diagnosis to first relapse, was shorter than the period between first and second relapse in 11/28 patients (40%). Toxicity was mild and oral PDN significantly increased the subjective tolerability of IFN. These findings indicate that IFN+GLU after induction chemotherapy may prolong the duration of tumor control in relapsed MM.