To clarify the role of high risk human papillomavirus (HPV 16, 18 and 33) and Epstein-Barr virus (EBV) infection in esophageal carcinogenesis in relation to expression of mutated p53 antioncogene, we used PCR to amplify DNA sequences of these viruses and immunohistochemistry to detect p53 expression in formaline-fixed, paraffin embedded blocks including 12 normal esophageal and 27 esophageal carcinoma specimens. HPV and EBV DNA were found in 25% and 0% of normal esophageal tissues and in 63% and 7% of esophageal carcinoma specimens, respectively. p53 expression was shown in 59% of esophageal carcinoma specimens only. HPV infection rate was significantly higher in specimens from carcinoma cases as compared with normal esophageal tissue obtained from cases without carcinoma. No correlation was found between p53 expression and/or the presence of viral DNA (HPV/EBV) in regard to the age and sex of the patient, histological grade, histological stage, depth of invasion, lymph node involvement, distant metastasis and the location of the tumors, p53 expression was almost equally distributed between HPV positive and negative carcinoma cases. Our results suggest that most of the esophageal carcinomas are associated with HPV infection and p53 mutations and there is no inverse correlation between HPV and infection and expression of p53 in esophageal carcinoma.