A randomized study compared the response of patients with multiple myeloma to chlorambucil, melphalan, and azathioprine. All patients also received a combination of prednisone and fluoxymesterone. Seventy-three of 86 patients entered on the study could have evaluations. The results indicate that melphalan produced more responses than either azathioprine or chlorambucil, but responses to both of these agents were observed. No difference was noted between survival curves for patients with no poor-risk factors as compared to those having at least one poor-risk factor. The only poor-risk factor affecting survival in this group of patients was the blood urea nitrogen level.