Barrett's mucosa is a potentially premalignant columnar lined metaplastic epithelium in the oesophagus about which little is known regarding maintenance of cell adhesion. In this regard E-Cadherin (E-cad) is a 120 kDa polypeptide present in all epithelial tissues and it is the prime mediator of cell-cell interactions. An immunohistochemical technique utilised the monoclonal antibody HECD-1 to evaluate E-cad expression in microwave treated, paraffin embedded sections from 120 patients. The phenotype of the specimens from the patients were metaplastic [41] and dysplastic mucosa [24], invasive squamous carcinoma [15] and adenocarcinoma [18] and corresponding metastatic lesions [10] as well as 12 specimens of normal oesophageal mucosae. Surface expression was high in non-metaplastic tissue and in non-dysplastic metaplasia but was reduced extensively in dysplasia. In addition in squamous carcinoma and adenocarcinoma E-cad was characteristically expressed in the cytoplasm and this was associated with poor morphological differentiation. SDS-PAGE gel protein analysis revealed the characteristic 120 kDa sized protein in normal squamous oesophageal tissue. In Barrett's metaplastic tissue and carcinoma, however, stronger bands at 108 kDa and 45 kDa were also present, suggesting either decreased glycosylation or a truncated protein in the metaplastic and neoplastic tissue, respectively. In conclusion changes in E-cad immunoreactivity and cellular localisation occur in premalignant metaplastic epithelium of the oesophagus. Further studies are in progress to evaluate whether the abnormal E-cad protein reflects both loss of function and may be used as a biomarker in pre-malignant lesions.