The levels of p53 protein were detected by immunocytochemistry in 197 endoscopic biopsy specimens of esophagus. Nuclear p53 protein was present in 2.9% of normal mucosa, 6.7% of inflammatory mucosa, 38.8% of mild dysplasia, 52.0% of moderate or severe dysplasia, 61.1% of carcinomas in situ, 62.5% of invasive carcinomas. Moreover, we examined 14 cases of esophageal carcinoma with extensive dysplasia near the carcinoma and found high levels of p53 protein in both dysplasias and carcinomas in 8 cases. In one case, carcinoma presented high level of p53 protein while the adjacent dysplasia did not. In another case, the result was just the opposite. Negativity for p53 immunostaining was found in 4 cases. These data indicated that p53 protein accumulation occurred before tumor invasion in the multistage esophageal carcinogenesis. The timing and the frequency of p53 protein accumulation made p53 gene an attractive marker for the early diagnosis an the evaluation of chemopreventive agents.