A transforming gene was cloned from a focus of rat fibroblast cell line Rat 1 transfected with DNA of a gastrocarcinoma cell line. The transforming gene is the activated form of oncogene c-Ha-ras, and the lesion was identified as a single nucleotide substitution at codon 12 by sequencing. We further used polymerase chain reaction (PCR)-restriction analysis to detect the mutations at codon 12 of c-Ha-ras. By using this method, 11 cases out of 24 solid tumors and 3 cell lines of gastric cancer were shown to contain mutations, and there was a strong correlation between mutations and metastasis and survival of the patients. The role of the activated c-Ha-ras in tumorigenesis of stomach cancer was further proved through the assay in which the malignant phenotypes of the c-Ha-ras-transformed cells were partially inhibited by blocking the c-Ha-ras expression with antisense oligonucleotides or exogenous plasmid expressing antisense RNA.