BACKGROUND. The goal of the current report was to demonstrate the long-term efficacy of outpatient subcutaneous (sc) interferon ␣ (IFN-␣) and sc interleukin 2 (IL-2)-based combination regimens in patients with metastatic renal cell carcinoma. METHODS. In three consecutive clinical trials, 443 patients received combined sc IFN-␣ and sc IL-2 (n ϭ 97 patients); combined sc IFN-␣, sc IL-2, and intravenous (iv) 5-fluorouracil (5-FU) (n ϭ 260 patients); or combined sc IFN-␣, sc IL-2, and iv 5-FU with oral 13cis-retinoic acid (n ϭ 86 patients). RESULTS. The median overall survival was 21ϩ months. The 2-year, 5-year, and 13-year survival rates were calculated at 45.26%, 15.96%, and 8.96%, respectively. The median time to disease progression was 6 months. The 2-year, 5-year, and 13-year progression free survival rates were 17.84%, 9.54%, and 9.20%, respectively. CONCLUSIONS. The current data suggest that combined outpatient sc IFN-␣ and sc IL-2, according to the Atzpodien regimen, achieves long-term survival benefits in a subset of patients with metastatic renal cell carcinoma, both with and without 13-cis-retinoic acid and/or 5-fluorouracil. Cancer 2002;95:1045-50.