AIMS: To examine CD44H and CD44v3 expression in normal gastric and small bowel mucosa, normal and Barrett oesophagus, and oesophageal epithelial malignancies (squamous cell carcinoma and adenocarcinoma). METHODS: Ninety five specimens, comprised of 40 of normal oesophageal, gastric and small bowel mucosa, 22 of Barrett oesophagus (two with dysplastic changes), 20 of resected adenocarcinomas, and 13 of squamous cell carcinoma, were evaluated. The samples were fixed in formalin and subsequently stained with anti-CD44H and anti-CD44v3 monoclonal antibodies using the avidin-biotin peroxidase technique. RESULTS: In contrast to normal oesophagus, which showed positivity for both CD44 epitopes (CD44H and CD44v3) in the basal third of the epithelium, antral and intestinal subtypes of Barrett oesophagus expressed CD44H only, the distribution being focal in non-dysplastic and diffuse in dysplastic Barrett mucosa. Similarly, normal antral glands and small bowel epithelium were focally immunopositive for CD44H at the base of the crypts. All squamous cell carcinomas were diffusely positive for both isoforms, whereas 75% (15/20) of the adenocarcinomas expressed CD44H and 60% (12/20) expressed CD44v3. CONCLUSIONS: CD44H is expressed in the proliferating areas of both normal squamous epithelium and Barrett mucosa. CD44H expression seems to increase progressively in dysplasia and infiltrating carcinoma, similar to the process described in the stomach. CD44v3 expression, usually not observed in normal or neoplastic gastric mucosa, was present in normal squamous epithelium and oesophageal squamous cell carcinoma. CD44v3 immunoreactivity was also identified in 60% of adenocarcinomas. These findings suggest that CD44v3 may play a role in the development of oesophageal carcinoma of both squamous and glandular types.