Alterations of the p53 and Ki-ras genes were examined in 12 human pancreatic cancer-derived cell lines with different metastatic potential. Point mutations of the Ki-ras gene at codon 12 were found in 10 out of 12 cell lines (83%), while abnormalities of the p53 gene were identified in 8 out of 12 cell lines (67%) which included point mutations (n=7) and one base deletion (n=1). The comparison between alterations of the p53 and Ki-ras genes showed that all the 12 cell lines revealed alterations of both genes or one of these genes regardless of the metastatic potential. Further, same alterations of the Ki-ras gene or p53 gene were noted among the cell lines with increased metastatic potential and their parental cell lines. These findings suggest that alterations of the p53 gene, like the Ki-ras gene is a frequent event in pancreatic cancer, and could contribute cooperatively in the oncogenic steps of pancreatic cancer. It is also suggested that the genetic changes of the p53 and Ki-ras genes are not substantially associated with the metastatic potential in pancreatic cancer.