Of 183 patients with multiple myeloma treated with melphalan, 43% demonstrated an objective response. Of the evaluable cases, 70% of the patients responded to combination therapy with melphalan and prednisone, 35% to intermittent melphalan therapy, and 19% to daily melphalan therapy. Symptomatic manifestations of disease decreased in almost all responding patients. The degree of remission was superior with melphalan-prednisone therapy since serum myeloma globulin peaks disappeared more frequently from the electrophoresis scan. In patients producing only λ Bence Jones proteins, azotemia was more frequent, the incidence of response was low, and survival was short. Median survival for patients treated with melphalan-prednisone was about six months longer than the survival of patients treated with melphalan alone. Results support the use of intermittent courses of concurrent chemotherapy with large doses of melphalan and prednisone in patients with multiple myeloma.