Eighty-five prostate cancer specimens from prostate resections were analyzed for the presence of p53 gene mutations by immunohistochemical staining for P53 protein. DNA from thirty-four of these samples was also analyzed for mutations in exons 5-8 by single-strand chain polymorphism (SSCP) analysis. One sample had P53 staining by immunohistochemistry, one sample was positive for a p53 mutation by SSCP, and one sample was positive by both techniques. Mutations in the two samples that were positive by SSCP were confirmed by nucleotide sequencing. In a separate study of ten lymph nodes that contained prostate cancer metastases, one had detectable P53 protein by immunohistochemical staining. Therefore, p53 mutations appear to be low frequency events in primary prostate cancer.