Abstract A total of 18 patients with non-Hodgkin's lymphoma who had progressed on or relapsed following total body irradiation were treated with chemotherapy. Before January 1972, patients were treated with vincristine alone. Since 1972, patients have been treated with combination chemotherapy; 10 patients have received cyclophosphamide, vincristine, prednisone (CVP); and two patients have received cyclophosphamide, vincristine, procarbazine, prednisone (C-MOPP) combination chemotherapy. An additional 2 patients had irradiation-compromised bone marrow reserves and were treated with prednisone and low dose CVP respectively. The overall response rate to chemotherapy was 66%. The amount and duration of chemotherapy did not appear to affect the responsiveness of the tumor to drugs, and a valuable determinant of this response was the underlying histology of the tumor. Non-Hodgkin's lymphomas, particularly the lymphocytic varieties, may remain responsive to chemotherapeutic agents despite extensive prior radiation therapy.