The cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine (COP-BLAM) programs of combination chemotherapy were administered to patients with advanced diffuse large cell lymphoma. The original COP-BLAM programs were designed to deliver intense multidrug therapy maximizing tumor kill. COP-BLAM programs IA and IB, easily administered on an outpatient basis, produced identical 73% complete remissions (CRs) and 55% long-term, disease-free survival (DFS). COP-BLAM III, an outgrowth of studies using infusional therapy, differed from COP-BLAM by using infusional bleomycin and vincristine alternated with bolus vincristine. With COP-BLAM III, 84% CRs, 76% "potential cures," and a 65% DFS were produced at a median follow-up time of 50 months. COD-BLAM IV, using four sequential cycles of infusional chemotherapy, high-dose alternating myelosuppressives (doxorubicin, cyclophosphamide), and cycle-active agents (methotrexate, cytarabine, and etoposide) produced 88% CRs, 67% potential cures, and a 64% DFS at a median follow-up of 24 months. COP-BLAM V employs four to six sequential cycles of infusional chemotherapy tailored to the rapidity of response. Preliminary results in patients with high-risk Hodgkin's disease suggest COP-BLAM V may be effective despite the shortened treatment time. In all programs, prognostic factors were critical determinants in the results achieved, particularly age and rapidity of response.