A phase II study was performed in a multicenter community setting of EPOCH (etoposide/doxorubicin/vincristine/cyclophosphamide/prednisone) chemotherapy in 93 patients with relapsed non-Hodgkin's lymphoma. Patients included 41 females and 52 males, ranging in age from 31-81 years (median, 63 years). Lymphoma histologies included diffuse large-cell (56), follicular (21), mantle cell (11), peripheral T-cell (3), and small lymphocytic (2) lymphomas. Patients had received a median of two previous chemotherapy combinations (range, 1-9). Most patients had received the drugs in EPOCH with their previous chemotherapy regimens (vincristine 97%, cyclophosphamide 97%, doxorubicin 87%, and etoposide 28%). A total of 350 cycles of EPOCH were administered. EPOCH chemotherapy gave a response rate of 51% in the entire cohort of 93 patients. Among the 83 evaluable patients, a response rate of 57% was observed (24% complete response, 33% partial response). Seven of the 47 responders remain in clinical remission at 3 years after EPOCH chemotherapy alone. Additionally, 11 patients are alive after further salvage chemotherapy (four patients) or bone marrow transplantation (seven patients). Myelosuppression was common, with 36% of all cycles resulting in an absolute neutrophil count nadir < 500/microL. This study confirms the activity of infusional chemotherapy with EPOCH in patients with relapsed non-Hodgkin's lymphoma.