A randomized multicenter phase III study was conducted to compare the efficacy and toxicity of CHOP and CNOP in intermediate and high-grade non-Hodgkin's lymphoma. CHOP consisted of cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, doxorubicin 50 mg/m2 on day 1 and prednisone 50 mg/m2 on days 1 to 5. The CNOP regimen was identical to CHOP except for replacement of doxorubicin by 10 mg/m2 mitoxantrone. Patient characteristics were evenly distributed in the two arms, except for age and stage, which slightly favoured the CHOP arm. The rate of complete remission was 70% (31/44) in patients treated with CHOP and 51% (23/45) in those receiving CNOP (P = 0.09). At 48 months and with a median follow-up of 41 months, 44% of the complete responders treated with CHOP and 64% of those treated with CNOP were estimated to still be in their first complete remission (P = 0.14), while 31% and 34% remained alive and free of progression. The Kaplan-Meier estimate of overall survival at 48 months is 53% and 50%, respectively. The higher response rate obtained with CHOP probably reflected a less aggressive lymphoma population. The mean WBC nadir was 2.0 x 10(9)/l for CHOP and 1.8 x 10(9)/l for CNOP. One and three patients, respectively, died during induction. Nausea, vomiting and cardiac toxicity were similar. More alopecia and mucositis were observed with CHOP. We conclude that CHOP and CNOP have similar toxicities and are equivalent in previously untreated non-Hodgkin's lymphoma in terms of complete response rate, event-free survival and overall survival.