A total of 296 evaluable patients with unfavorable categories of malignant lymphoma were randomly assigned treatment with cyclophosphamide, vincristine, and prednisone plus BCNU (BCOP) or doxorubicin (CHOP). In diffuse histiocytic (DH) lymphoma, CHOP produced superior complete (54% v 34%) and total (70% v 46%) response rates. Among the responders to either therapy, no differences were seen in duration of response or survival times. Median duration of response has not been reached with follow-up in excess of 50 months. In categories of lymphoma other than DH (including small-cell, mixed, and nodular histiocytic lymphomas), complete (27% v 29%) and total (48% v 54%) responses were similar for BCOP and CHOP, as were durations of response and survival. These data suggest that BCOP and CHOP are equivalent regimens for other categories of malignant lymphomas. CHOP appears preferable for diffuse large-cell categories, since it resulted in greater overall survival in patients with DH lymphoma; this was due to a significantly greater response rate, since patients with DH lymphoma who did respond to BCOP maintained their response and survived as long as did the CHOP responders.