Epidemiological studies have demonstrated an association between human esophageal cancer and dietary/nutritional risk factors in developing countries. We examined the expression of p53 protein in 51 cases of esophageal squamous cell carcinomas (ESCCs) and paired normal esophageal tissues by immunohistochemistry. Alterations in the tumor suppressor gene p53 (exons 5-8) were analyzed in 51 cases of ESCC and paired normal tissues by PCR and single-strand conformation polymorphism. p53 protein expression was correlated with major dietary risk factors and common carcinogens identified in India. Immunohistochemical analysis of frozen esophageal tissue sections using anti-p53 monoclonal antibody (D0-1) showed overexpression of the protein in the nuclei of epithelial cells in 39 of 51 (76%) cases. The histopathologically proven normal esophageal tissue sections taken from a distant site from esophageal cancer patients did not show any detectable level of p53 immunoreactivity. The PCR-single-strand conformation polymorphism analysis showed a mobility shift in 37 of 51 (72%) ESCCs. Intake of chilies was positively associated with p53 protein expression (P < 0. 01) in the esophageal cancerous lesions. Our results suggest that p53 alterations are frequent events in esophageal oncogenesis in the Indian population, which has dietary habits that are considerably different from those of the Western population.