Five partial responses were seen in 23 patients with metastatic renal-cell carcinoma (MRCC) receiving interferon-alpha 2a (IFN)+prednisone (P). Four of 24 subsequent patients responded to IFN+P (combined response rate 19%). The median response duration was 8 months (3 to 30 months). The one-year survival for all eligible patients was 52%. Eight of 26 evaluable patients developed antibodies detected by an enzyme immunoassay. In 2 patients, high levels of neutralizing antibodies were also found, together with particularly low IFN levels. In one patient the development of neutralizing antibodies coincided with the loss of initial response. The treatment was well tolerated by most patients. Premature discontinuation of treatment was necessary in only 2 patients. In MRCC, combination treatment with IFN+P is as effective as IFN monotherapy (response rate 19%), with significantly reduced subjective toxicity. The clinical relevance of the development of antibodies against IFN requires further investigation.