The Eastern Cooperative Oncology Group has studied 113 patients with generalized progressive malignant lymphomas i n a randomized clinical trial. Pathologic diagnosis was subclassified by cell type and nodal pattern by The Pathology Panel for Lymphoma Clinical Trials. Patients were randomly assigned treatment with either cyclophosphamide (C) , vincristine (0) , and prednisone (P) (COP) or C O without prednisone. Initial treatment was given for 8 weeks and further randomization of responders to observation or additional chemotherapy was carried out. A significant difference in complete remission rate between treatments was shown: with COP, 43%, and with CO, 17%, indicating an important role for prednisone in inducing CR. COP was also associated with longer remission durations and improved survival. Complete remission following initial chemotherapy is also associated with longer duration of disease-free time and survival. The initial pathologic cell types and nodal pattern also strongly influence survival. Extended "maintainence" C O treatment improved disease-free remission duration, but not survival. Cancer 38:1052-1059, 1976. OMBINATION CHEMOTHERAPY OF ACUTE LEU-C kemia, Hodgkin's disease, and the malignant lymphomas has been demonstrated repeat-'l'his study was undertaken by the Eastern Cooperative Investigations were supported by Public Health Service