Nine human melanoma cell lines established in our laboratory were analyzed for p53 gene expression and their tumorigenic and metastatic potential in nude mice. Northern blot analyses showed that five of the cell lines (55%) had either complete loss or low levels of p53 transcripts. Immunocytochemical analysis for p53 protein expression agreed with mRNA analysis results. Nucleotide sequencing showed no mutations in exons 5 through 8 of the gene. All cell lines except one gave rise to tumors at subcutaneous inoculation sites in nude mice. The melanoma cell line UISO-MEL-6, completely lacking p53 expression, spontaneously metastasized to lung and liver in nude mice.