Interleukin-2 (IL2) or/and interferon (IFN) are routinely used for treating patients with metastatic renal cell cancer. However, results are disappointing since most patients experience treatment failure. Within 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 treatment response or failure. We identified two independent factors predictive of response to cytokine treatment: having only one metastatic organ site and receiving a combination of cytokine treatments. We also identified four independent factors predictive of rapid progression under 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 combine at least three of these factors have over 80% probability of rapid progression despite treatment. We think that these results must be taken into account for cytokine treatment decision.