Point mutations of c-Ki-ras genes were analyzed in 33 samples of human gastrointestinal malignancy. DNA extracted from the frozen tissue was amplified by polymerase chain reaction (PCR) and analyzed by direct sequencing and slot-blot hybridization at codons 12, 13 and 61 of c-Ki-ras. In 7 cases out of 19 colorectal cancers, point mutations were found: 3 cases at codon 12, 1 at codon 13, 2 at codon 61 of c-Ki-ras and one case had double mutations at codon 12 and codon 13. In 11 cases of gastric cancer, 4 showed point mutations: 1 at codon 12 and 3 at codon 13 of c-Ki-ras. In 3 pancreatic carcinomas, 2 had point mutations: one at codon 12 and the other at codon 13 of c-Ki-ras. The results indicate that c-Ki-ras gene point mutations are involved in the tumorigenesis of the human gastrointestinal system.