Interferon-α has been used to treat advanced renal cell carcinoma, and megestrol acetate has been shown to improve the quality of life of patients who have cancer. We combined interferon α-2b, 10 million IU/m2 subcutaneously 5 consecutive days per week, with megestrol acetate, 80 mg orally twice a day, in 15 patients who had advanced renal cell carcinoma. Only 6 (40%) had a prior nephrectomy, and most had disease in the lung and other sites. There were no complete or partial responders to this treatment, although stable disease was achieved in 5 (33%) patients. The treatment was excessively toxic, with 12 (86%) patients requiring dose modification or discontinuation of treatment due to fatigue. We conclude that interferon α-2b and megestrol acetate is an excessively toxic, inactive regimen, at least in a group of patients who have advanced disease with a poor prognosis.