This report describes a phase II Eastern Cooperative Oncology Group (ECOG) study of high-dose lymphoblastoid interferon (IFN alpha-n1) in 39 patients with measurable, advanced renal cell carcinoma. The original treatment plan was 30 X 10(6) units/m2 (30 mU) of IFN alpha-n1 im daily X 10 days; treatments were repeated every 21 days. This dose and schedule proved intolerable, with none of seven patients able to complete greater than 10 days of therapy because of fever, lassitude, hepatic dysfunction, and myelosuppression. Patients were subsequently treated with the following regimen: 3 mU/m2 on Day 1; 5 mU/m2 on Day 2; 10 mU/m2 on Day 3; and 20 mU/m2 on Days 4-10. Thirty-three new patients received this regimen and two patients received this schedule after having received 30 mU/m2. Using this second regimen, 30% of the patients were able to complete two cycles of treatment without dose reduction or interruption. Five patients (13%) had partial response (ECOG criteria) of measurable tumor. Median time to response was 140 days. Responses were documented in lung metastases in four patients and in a pelvic soft tissue mass in the fifth. Response rates and survival times are similar to those seen in prior ECOG phase II trials in advanced renal cell carcinoma. Eight of 39 patients are still alive greater than 2 years after beginning therapy. Only two of these patients had had an objective response, however. Such prolonged survival is more frequent than has been seen in previous ECOG studies. The relative contribution of patient selection and interferon therapy to this survival is uncertain.