Oesophageal epithelium is frequently exposed to various carcinogens and mutagens, many of which may cause p53 gene mutations. The epithelium can also be infected with human papillomavirus (HPV), the E6 protein of which may complex with p53 protein and facilitate its degradation. To identify HPV infection and p53 overexpression in oesophageal cancer, we performed immunohistochemical analysis using CM-1 anti-p53 antibody and DNA in situ hybridization with biotinylated HPV DNA probes on paraffin-embedded sections in 36 patients with oesophageal squamous cell carcinomas derived from a high-incidence area in northern China. Samples from cancer tissue, adjacent epithelia, regional lymph nodes as well as resection margins were examined. p53 protein accumulation was detected in 55.6% (20/36) of cancer samples, in 20% (1/5) of hyperplastic epithelium, in 20% (2/10) of dysplastic lesions as well as in 67% (2/3) of carcinoma in situ lesions adjacent to invasive carcinomas. HPV DNA sequences were demonstrated in 3 patients (8.3% of the total). Two of these HPV-positive carcinomas were immunohistochemically negative for p53 and one was weakly positive. Our results suggest that p53 overexpression is frequently found in oesophageal carcinomas and that p53 alteration may be an early event in esophageal carcinogenesis. HPV and elevated p53 are not mutually exclusive events, instead they can coexist in some oesophageal squamous cell carcinomas.