The effects of various regimens of melphalan combination chemotherapy were evaluated in 508 patients with multiple myeloma. No value was confirmed from the addition of procarbazine or vincristine sulfate to melphalan-prednisone combinations. Ninety-six patients who responded to treatment were allocated at random to one of three maintenance regimens, namely intermittent courses of carmustine with prednisone, continued courses of melphalan with prednisone, or no chemotherapy. There were no differences in the frequency of relapse, the remission duration, or the survival time among these maintenance groups. The frequencies of pneumonia and herpes zoster were higher in patients receiving continued chemotherapy. Continued melphalan-prednisone chemotherapy after the first year is of no major value to responding patients with multiple myeloma. Attempts to reduce tumor mass maximally with a change in therapy are justified.