The association of interleukin-2 (IL-2), interferon alpha-2a (IFNalpha), 5-fluorouracil (5-FU) has been reported to induce response in metastatic renal cell carcinoma (MRCC). This study evaluated IL-2, IFNalpha and 5FU as second-line treatment after failure under immunotherapy. A total of 35 patients received IL-2, at 9 x 10(6) IU m(-2), once or t.i.d, 5 days a week, every other week. Interferon alpha was administered at 6 MUI, TIW along with IL-2 every week. 5-Fluorouracil was given at 750 mg m(-2) day(-1) on days 1-5 every 4 weeks. One cycle lasted 8 weeks. All patients were evaluable for response and toxicity. There were two objective responses (5.7%) and 14 stable diseases (40%). Survival was 14 months. In all, 17 patients experienced grade 3 toxicity. The predictive factor for progression to second-line immunotherapy was the results of first-line immunotherapy, and performance status, delay from primary tumour to metastases and response or stabilisation to chemo-immunotherapy for survival. IL-2, IFNalpha and 5-FU induce low objective response but stabilisation in patients with MRCC having failed with immunotherapy, and may be considered only in selected patients on performance status, stabilisation or response after first-line immunotherapy and interval from their primary tumour to metastases.