We have examined the activity of protein tyrosine phosphatase in various tumor cell lines and surgically resected human colon carcinoma specimens. The protein tyrosine phosphatase activity of rat fibroblasts increases with the transformation by v-src gene. Likewise human colon carcinoma and human neuroblastoma cell lines, in which the activation of c-src tyrosine kinase was reported, show elevated protein tyrosine phosphatase activity in most cases. We compared the protein tyrosine phosphatase activity of eight human colon cancer tissues with that of normal mucosa of the same patient. The results show that the protein tyrosine phosphatase activity in tumor tissue was increased, suggesting the biological significance of protein tyrosine phosphatase in colon cancer.