AbstractIn 1968 the Cancer and Acute Leukemia Group B (CALGB) demonstrated optimal control of disseminated non‐Hodgkin lymphomas (NHL) with vincristine‐prednisone induction followed by cyclophosphamide maintenance. A study was then begun to determine whether four drugs in combination or sequence could achieve greater control. NHL patients at each participating CALGB institution were randomly assigned to one of three regimens: I) Cyclic vincristine‐streptonigrin alternating every 2 weeks with cyclophosphamide‐prednisone up to 155 days; II) Sequential treatment with the same 4 drugs taken singly up to 182 days; and III) Vincristine‐prednisone induction for 6 weeks followed by cyclophosphamide maintenance. Results are now reported after a 10 year follow‐up period. The 203 evaluable patients are those on whom Rappaport histopathologic classification was available. Frequency of complete response did not differ significantly among the three regimens: I) 38%; II) 30%; and III) 45%. Remission durations were significantly longer among patients receiving maintenance therapy. After ten years, two patients from Regimen I, one from Regimen II, and five from Regimen III remain alive and well. It was concluded that neither of the four‐drug regimens conferred a significant advantage in terms of response rate or survival time over the stand