Multiple drug programs were used to treat patients with stage IIIB and IV Hodgkin's disease and lymphosarcoma. These consisted of combinations of full doses of vincristine sulfate, cyclophosphamide, and prednisone and either mercaptopurine or procarbazine hydrochloride given as three to five 10-day courses with 11-day intervals between courses. No maintenance therapy was given. The complete remission rate in previously untreated patients was 90%, while only 26% of patients who had relapsed following previous therapy achieved remission. Remission durations ranged from 3 to 17 months with a mean of 7 months. The results indicate that multiple drug therapy programs provide prolonged and dramatic remissions in many patients with widespread lymphoma, and their use is recommended in critically ill patients. Whether the results in less critically ill patients are superior to those obtainable with single drugs used sequentially is not established.