Chemoimmunotherapy (CIT) with interleukin-2, interferon-alpha2a, and 5-fluorouracil is an accepted treatment option of metastatic renal cell carcinoma (mRCC). Because of the enhancement of the antiproliferative effects of interferon-alpha2a, 13-cis-retinoic acid (13-CRA) might be of potential usefulness for immunotherapy. We have investigated the effect of 13-CRA in patients treated with chemoimmunotherapy. Seventy-two patients with mRCC and a Karnofsky performance index > or = 80% were retrospectively analyzed. Thirty-six patients received chemoimmunotherapy and 36 other patients were treated similarly but with addition of daily 60 mg 13-CRA. Response was assessed according to the UICC criteria. Survival was calculated by Kaplan Meier estimation and compared with the log-rank test. In the CIT group objective remissions occurred in 34.3% (95% CI 19.1-52.2) and stabilizations in 42.9% (median follow-up 16 months). In the CIT plus 13-CRA group, objective remissions were seen in 26.4% (95% CI 12.9-44.4) and stabilizations in 50% (median follow-up 17 months). One- and three-year survival rates were 76% and 32% in the CIT group and 82% and 37% in the CIT plus 13-CRA group. The combination of CIT and 13-CRA did not significantly differ in objective remissions and estimated survival compared with CIT. Our retrospective data suggest that 13-CRA does not enhance the therapeutic efficacy of CIT in mRCC patients with a good performance status.