Combination chemotherapy and radiotherapy (RT) were administered to 73 adults with non-Hodgkin's lymphoma (NHL). Ten cycles of the following drugs were given: intravenous Adriamycin (doxorubicin) (25 mg/m2), cyclophosphamide (700 mg/m2) and vincristine (1.5 mg/m2) on day 1; arabinosylcytosine (100 mg/m2) and methotrexate (10 mg/m2) on days 3 to 5; and oral prednisone (60 mg/m2) on days 1 to 5. Radiotherapy was given to resistant or initially bulky disease (2000 rad). Patients were also randomized to receive pseudomonas vaccine or no immunotherapy. Of 61 evaluable patients, 33 (54%) achieved a complete response (CR) and 18 (30%) a partial response (PR). Among 44 evaluable patients with diffuse histiocytic lymphoma (DHL), 22 (50%) had a CR, and 15 (34%) a PR. For 17 evaluable patients with nodular (4) and diffuse (11) mixed and poorly differentiated lymphocytic and diffuse "undifferentiated" (2) lymphomas, CR and PR rates were 65% and 18%, respectively. No statistically significant differences in response rate or duration and survival have been observed between the patients randomized to receive pseudomonas vaccine or no immunotherapy. Median follow-up time from start of treatment was 47.5 months. Median survival for all 73 patients (including inevaluables ) and for 52 DHL patients was 30.7 months. Poor prognostic features influencing survival included: female sex (P = 0.003), poor response to therapy (CR versus PR; P = 0.001), prior chemotherapy, (P = 0.01) and high levels of lactic dehydrogenase (P = 0.001). It can be concluded that this combination of cycle and phase-active agents is of similar efficacy to other reported regimens in inducing major responses and that it has the potential to prolong disease-free survival. The analysis of prognostic factors has been used to dissect poor prognostic categories that might require different modalities of treatment.