Alpha-interferon (IFN) has been shown to produce antitumor responses among patients with advanced renal cell carcinoma. While responses have been observed over a range of IFN doses and schedules, significant toxicities can be experienced from relatively high doses given three to five times weekly. Based upon the report of a pilot study indicating that low dose daily IFN could produce antitumor responses with minimal toxicity, the Southwest Oncology Group investigated this schema in a phase II trial. Patients with bidimensionally measurable disease were treated with Roferon-A 1 million units subcutaneously daily and tumor assessments were conducted on a monthly basis. There were no dose escalations and no dose reductions for toxicity. The treatment was well tolerated with only two patients withdrawing from treatment because of side effects. Among 56 eligible patients treated, there were five partial responses and one complete response for an overall response rate of 11% (95% confidence interval, 4 - 22%). However, objective antitumor responses could not be determined for 16 of the 56 patients. Among the 40 fully evaluable patients the 6 objective responses yields a response rate of 15% (95% confidence interval, 5.7-30%). It is concluded that this dose and schedule of IFN has activity against advanced renal cell carcinoma. A randomized trial would be required to determine if this low dose regimen is as effective as the higher doses which have been used traditionally.