p53 gene alterations in ten gastric adenomas and one carcinoma arising in an adenoma were analyzed by deoxynucleotide sequencing. Three (30%) of the ten gastric adenomas had p53 gene mutations, one adenoma showing a frameshift mutation and two others showing silent mutations. In addition, two missense mutations occurred in the carcinoma arising in an adenoma. Histologically, the adenomas containing silent mutations revealed moderate dysplasia. Immunoreactivity to p53 protein was also examined in 61 gastric adenomas, 19 carcinomas arising in adenomas and 48 early well-differentiated adenocarcinomas of the stomach (these included the tumors analyzed by deoxynucleotide sequencing). No staining for p53 was seen in the pure adenomas, but positive immunoreactivity was observed in 27% of the adenocarcinomas and 10.5% of the carcinomas arising in adenomas. These results suggest that p53 gene mutation is an early event in gastric carcinogenesis and missense mutation may play a crucial role in the conversion from adenoma to adenocarcinoma.