Point mutations at the 12th codon of c-Ki-ras in pancreatic cancer from Japanese patients were examined using the polymerase chain reaction, followed by cloning of the amplified gene fragments in pTZ phagemid and nucleotide sequence determination. The frequency of the point mutations found in the tumors was quite high (75%). The mutation most frequently detected was a G---A transition at the second position of codon 12 (GGT---GAT), but other types of mutations such as GGT----GTT and GGT----CGT were also found. In one case, silent mutation of GGT to GGC was detected in addition to the frequent mutation of GGT to GAT. These observations suggest that the 12th codon of pancreatic c-Ki-ras is highly mutatable.