Twenty-five patients with Stage III and IV nodular histiocytic lymphoma (NH), entered on three different Eastern Cooperative Oncology Group protocols from 1972-78, were analyzed for response and survival. A complete response (CR) rate of 44% was observed, with 40% partial responders (PR). Four of the 11 CRs are continuing in their original remission. Median survival for CRs was 52 months; for PRs it was 30 months. The six patients treated with cyclophosphamide-prednisone had a median survival of 18 months versus 51 months for the 19 patients treated with more aggressive combination chemotherapy programs. No significant difference in survival was noted between those patients with both nodular and diffuse histology and those with a pure nodular pattern. The median survival of the 25 NH patients was 47 months and is similar to a group of 101 patients with nodular mixed lymphoma (NM) entered on the same ECOG protocols during this time. This survival is intermediate between the nodular lymphocytic poorly differentiated subtype and diffuse histiocytic lymphoma. It suggests that patients with NH histologies be treated with aggressive combination chemotherapy programs designed to achieve complete remission and prolonged disease-free survival.