Between May 1986 and March 1991, 38 patients with previously untreated advanced intermediate and high-grade non-Hodgkin's lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B): 73% of the patients had stages III and IV disease, 55% had "B" symptoms, and 55% had bulky disease (nodal masses > 10 cm). Histologic subtypes included diffuse large-cell and immunoblastic lymphoma. In 96% of patients clinical response was achieved (69% complete response and 27% partial response). Acturial disease-free survival and overall survival were 55% and 60%, respectively, at 2 years. Treatment-related mortality was 16%: 3 patients died from neutropenic sepsis and 3 (hepatitis B carriers) from fulminant hepatitis at the time of steroid withdrawal. The incidence of nonfatal neutropenic fever was 24% and mucocutaneous toxicity was common. The poorer overall results may be attributed to more advanced disease. Caution is advised in the use of MACOP-B among hepatitis B carriers.