A randomized therapeutic trial of three induction regimens for patients with lymphosarcoma and reticulum-cell sarcoma was conducted by the Cancer and Leukemia Group B (CALGB) (formerly Acute Leukemia Group B.) Addition of streptonigrin, but not cyclophosphamide, to the combination of vincristine and prednisone improved the complete remission rate achieved after a 42-day induction program. The duration of the subsequent remission and survival was not influenced by the induction combination assigned. Remission maintenance with cyclophosphamide was superior to maintenance with methotrexate. The results of this study are compared with others in which advantages for three or four drug treatment regimens have been reported.