For the past 15 years, immunoreactive cytokines have been the mainstay of treatment for metastatic renal cancer. High-dose bolus interleukin-2 (IL-2) was granted US Food and Drug Administration (FDA) approval in 1992 based on its ability to produce durable complete responses (CRs) in a small number of patients. Unfortunately, the toxicity, expense, and restricted accessibility of high-dose IL-2 make it a poor standard therapy. Regimens involving lower doses of IL-2 either alone or in combination with interferon (IFN) have generally produced fewer tumor regressions and these regressions were of less overall quality. Recent efforts have focused on trying to identify factors predictive of response to IL-2 therapy so that this treatment can be limited to those most likely to benefit. This year, investigators will launch a clinical trial designed to prospectively determine if patients who are more likely to respond to high-dose IL-2 can be identified prior to starting therapy.