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Interleukin-2 (IL-2) or/and interferon (IFN) are routinely used for treating patients with metastatic renal cell cancer. However, results have been disappointing, with a majority of treatment failure. Over 6 years, the Groupe Français d'Immunothérapie enrolled 782 patients in successive multicenter trials using cytokine regimens. Univariate and multivariate analyses were performed on this large prospective database to identify prognostic factors for survival. The presence of biological signs of inflammation, short time interval from renal tumor to metastases (<1 year), elevated neutrophil counts, liver metastases, bone metastases, patient performance status (PS), the number of metastatic sites, alkaline phosphatases and hemoglobin levels were predictive of survival outcome. When compared with previous results, our study showed that PS, number of metastatic sites, disease-free interval, biological signs of inflammation and hemoglobin levels can be considered as validated prognostic factors. We also identified four independent factors predictive of rapid progression under cytokine treatment: presence of hepatic metastases, short interval from renal tumor to metastases (<1 year), more than one metastatic site and elevated neutrophil counts. Patients who combined at least three of these factors have >80% probability of rapid progression despite treatment. We think that these results must be taken into account when making the decision to treat with cytokine.