This clinical trial was designed to investigate if maintenance therapy with alfa-interferon could prolong the plateau phase in patients with multiple myeloma. In addition, the tolerability of interferon treatment and its effect on survival were evaluated. From September 1987 to September 1989 a total of 314 patients were accrued to a multi-institutional randomized clinical trial. All patients entered into the protocol received standard melphalan-prednisone (MP) induction therapy. Response was noted in 184 (59%) and a plateau phase achieved in 155 (49%). From the latter group, 125 eligible patients were randomized to either interferon alfa-2b or no maintenance. The patients were followed for an average of 51 months (minimum 36 months) from the time of randomization. The plateau phase was significantly prolonged in the group of patients treated with interferon (median 13.9 v 5.7 months from the time of randomization; P < 0.0001). The interferon therapy was tolerated fairly well, moderate granulocytopenia and a chronic fatigue syndrome being the most frequent side-effects (22% v 18% W.H.O. grade 3 toxicity). The median survival from randomization was almost identical in both groups (36 v 35 months). The study shows that interferon maintenance therapy given to multiple myeloma patients who have achieved a response to initial treatment with MP prolongs the plateau phase duration with tolerable toxicity. The clinical value of this finding should be interpreted with caution, because survival was not prolonged. Further studies are required to clarify the role of interferon in the treatment of multiple myeloma.