Mutations in codon 12 of K-ras occur in a high proportion of pancreatic cancer cases. Although there is evidence that p53 mutations also occur in this tumor, few studies have been reported to date and no comparison has been made of K-ras and p53 mutations in the same tissues. Single-strand conformation polymorphism and sequencing of the PCR products were used to determine mutations in p53 gene; to detect mutations in K-ras genes, the artificial restriction fragment length polymorphism (RFLP) approach was used. Eight out of 30 tissues from primary pancreas cancer and 3 of 4 samples from metastases showed p53 mutations. Fifteen out of 17 pancreatic cancer cell lines had p53 mutations. In 2 cases, the same p53 mutation was identified in the original tumor and in a tumor-derived cell line. The majority of p53 mutations were present in exons 5-9 of the gene. Mutations at codon 12 of the K-ras gene were identified in 23/32 pancreas cancer tissues and in 14/17 cell lines. There was no relationship between the types of mutation observed in the 2 genes. In conclusion, mutations in K-ras and p53 genes are common in pancreatic cancer. p53 mutations may occur more frequently in metastatic lesions than in primary tumors, although further work is necessary to investigate this point.