To assess the efficiency and toxicity of alternating combination chemotherapy plus interferon-alpha-2b (IFN) in the treatment of poor prognosis multiple myeloma, we began a prospective clinical trial. The study involved 103 previously untreated patients with poor prognosis: Stage III, haemoglobin below 8.5 g/dl, beta 2-microglobulin > 5.0 micrograms/ml and multiple lytic lesions. All patients were treated with an alternating combined regimen given monthly for 2 years. After randomization, 52 patients also received IFN at a dosage of 5.0 MU three times weekly during the first year of the therapy. The remaining 51 patients received chemotherapy alone. Compared with patients treated with chemotherapy alone, those treated with chemotherapy plus IFN had a higher overall rate of response: (80% versus 47%), a longer duration of remission (36 months versus 18.5 months) and a higher rate of survival at 5 years (74% versus 39%; P < 0.001). Toxicity was similar in both arms. All patients received the planned dose of IFN. There were no deaths related to treatment. The addition of IFN to a regimen of alternating chemotherapy increased the rate of response, duration of remission and survival in patients with poor prognosis multiple myeloma, without serious side effects.