The effect of recombinant interferon-alpha-2C monotherapy was compared with the efficacy of VMCP-polychemotherapy in 42 patients with multiple myeloma in a prospective randomized multicenter trial. IFN-treatment induced remissions (R) in 2 (14%) and partial remissions (PR) in 4 (29%) out of 14 evaluable patients. 7 patients remained stable. Polychemotherapy induced R in 11 (57%) and PR in 6 (32%) of 19 evaluable patients. 2 (11%) patients remained stable. IFN was preferentially active in patients with low tumor burden and patients with IgA paraprotein. The proportion of responders (R + PR) was significantly lower in the IFN-arm (43%) compared to the polychemotherapy group (89%; p less than 0,001).