Patients with non-Hodgkin's lymphomas are classified by the Working Formulation into low, intermediate, and high grade based on the aggressiveness of the lymphoma. Intermediate- and high-grade lymphomas are rapidly progressive, fatal diseases unless the patient achieves a complete remission after treatment with combination chemotherapy. Complete remissions have been reported in 40% to 80% of these patients, and 30% to 60% of these patients are actually cured. alpha-Interferon studies of relapsed patients have resulted in approximately a 15% objective response rate with only 2% complete remissions. Thus at this time alpha-interferon has no role in the treatment of these patients. Treatment of low-grade lymphomas with combination chemotherapy results in complete remission rates varying from 25% to 70%. However, these complete remissions are not durable and the patients essentially all relapse with a 22-month median duration of complete remission. In spite of these relapses, median survival for all patients exceeds 7 years. alpha-Interferon has shown beneficial clinical activity in the low-grade lymphomas. Overall response rates are approximately 46%, with 11% complete remission. There is some evidence to suggest that there is a useful dose-response curve, with the highest remission rates being seen at the highest alpha-interferon doses. The median duration of response is approximately 8 months. Combining alpha-interferon with standard chemotherapy has not resulted in an easily detectable improvement in response rate or duration. The role of alpha-interferon in prolonging remission duration for these low-grade lymphomas is being investigated by the Southwest Oncology Group. In summary, alpha-interferon has shown moderate activity when used to treat patients with low-grade non-Hodgkin's lymphomas.