We analyzed the status of retinoblastoma and p53 genes in 10 human hepatoma cell lines. Polyclonal anti-peptide antibodies generated against peptides homologous to COOH-terminal and leucine-zipper domains of the retinoblastoma protein allowed us to identify two cell lines (Hep 3B and FOCUS) with abnormal expression. The same cell lines have both lacked p53 expression. In contrast to the retinoblastoma gene, the expression of the p53 gene was abnormal in six additional cell lines. Indeed, only the Hep G2 hepatoblastoma cell line (and its derivative Hep G2/2215) appeared to have normal p53 and retinoblastoma gene expression. Our studies indicate that p53 abnormalities are common but retinoblastoma gene aberrations are rare in human hepatoma cell lines.