Primary hyperparathyroidism is a common disorder characterized by aberrant growth and function of solitary or multiple parathyroid glands. Many, if not all, parathyroid adenomas are examples of benign clonal neoplastic growth. The molecular events associated with the development of parathyroid neoplasia have not been well characterized. We examined benign and malignant parathyroid tissues for structural abnormalities of the p53 tumor suppressor gene. To screen for mutations in the p53 gene, we analyzed polymerase chain reaction-amplified DNA by denaturing gradient gel electrophoresis. DNA was isolated from 26 benign parathyroid adenomas and 3 parathyroid carcinomas, and polymerase chain reaction was used to amplify DNA fragments corresponding to the 4 evolutionarily conserved domains within exons 5, 7, and 8 of the p53 gene in which the majority of point mutations have been identified. Amplified DNA fragments were electrophoresed through polyacrylamide gels with linearly increasing gradients of the denaturants urea and formamide. After electrophoresis, the gels were examined for the presence of abnormally migrating bands, which represent DNA with altered melting points due to nucleotide sequence changes. Amplified fragments were of the expected size in DNA from 26 parathyroid adenomas and 3 parathyroid carcinomas. Denaturing gradient gel electrophoresis studies failed to disclose evidence of mutations in exons 5, 7, and 8 of the p53 gene in these neoplasms. We conclude that p53 point mutations do not appear to be a primary event responsible for neoplastic growth in parathyroid tissue.