Interferon-alpha is an accepted treatment for renal cell carcinoma, with a response rate approximately 14%. Retinoic acid has been claimed to improve such a response rate when combined with interferon. We present the results of a phase II study combining interferon alpha and all-trans retinoic acid (ATRA) in patients with metastatic renal cell carcinoma. Thirty-one patients who were not eligible for a trial of high-dose interleukin-2 treatment (because of low performance status: 7 patients; prior immunotherapy: 11 patients; age > 70: 8 patients, cardiac or respiratory failure: 4 patients; refusal for randomization: 1 patient) were enrolled in this study. Only one partial response was observed (3%). Despite the good tolerance observed with this association, ATRA does not improve the efficacy of interferon in this selected patient population (with poor prognosis). Such a treatment combination should not be further recommended in patients with metastatic renal cell carcinoma.