To investigate the importance of oncogenes and tumor suppressor genes in bladder carcinogenesis, we determined the status of the expression of the MDM-2 and p53 genes and genetic alterations in the p53 gene in five bladder carcinoma cell lines and one kidney urothelial carcinoma cell line. Overexpression of MDM-2 mRNA was observed in three bladder carcinoma cell lines, J82, SCaBER, and BFTC-905. Amplification of the MDM-2 gene was not detected in any of the six cell lines by southern analysis. The deletion in the p53 gene was observed in J82, and point mutation was detected in J82 and BFTC-909, the kidney urothelial carcinoma cell line. In contrast, no mutations were found in codons 12, 13, and 61 in the Ha-ras and Ki-ras genes in these six cell lines. These results indicate that alterations in the p53-regulated pathway are important in bladder carcinogenesis.