The p53 tumor-suppressor gene is the most commonly mutated gene in cancer. However, p53 gene alterations are infrequent in renal-cell cancer (RCC). Bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53 and an inverse correlation between Bcl-2 expression and p53 mutation has been observed in breast cancer and glioma. To characterize the expression of bcl-2 in RCC and its relationship to the p53 status, we analyzed 25 RCCs by immunohistochemistry for Bcl-2 and p53, Southern hybridization for bcl-2, and PCR-SSCP and sequencing for p53. Positive Bcl-2 staining was detected in 17 of 25 RCCs, whereas positive p53 staining was seen in only 1. Amplification of bcl-2 or p53 mutation was not detected in any of the tumors. Bcl-2 protein was expressed in all 7 RCC cell lines examined. Only one of the 7 lines had p53 mutation. These results suggest that overexpression of bcl-2, rather than p53 mutation, may prevent apoptosis during RCC development.