The distinctive biology of renal cell carcinoma and its low response to conventional therapies have prompted researchers in this field to search for other therapeutic strategies. In this paper we describe the current concepts regarding the biology of this neoplasia and new therapeutic perspectives for this disorder, with particular interest in the use of biological response modifiers, including alpha-interferon (alpha-IFN). In view of the evidence of spontaneous regressions of metastases observed after nephrectomy, a possible role of the immune system has been hypothesized in modulating the natural course of renal cell carcinoma. In this context, several groups have focused their attention on the immunotherapeutic approach to this disease. Major biological characteristics of alpha-IFN are reported here, with particular attention paid to its immunomodulatory properties. As a matter of fact, significant results have been obtained by using this molecule, either alone or in association with chemotherapeutic agents (vinblastine). In this paper we focus on the efficacy of these therapeutic approaches by reporting the data obtained from the major clinical trials in which alpha-IFN has been used, including a personal series of cases.