E-cadherin, an epithelial adhesion molecule, is critical for the maintenance of cell polarity and differentiation. We studied the distribution of E-cadherin in normal gut and in enteric ulceration to test the hypothesis that the motility of regenerative epithelium over ulcers is associated with a decrease in E-cadherin expression. Sections of normal stomach, small intestine, and colon were examined for E-cadherin distribution using the antibody HECD-1 and compared with the pattern seen in peptic ulceration and Crohn's disease. A subset was examined by in situ hybridization using 35S radiolabeled E-cadherin riboprobes. A wounding system employing the HT-29 cell line was used as an in vitro model of early healing. In the normal gut uniform strong basolateral staining was seen. Areas of ulceration showed a patchy reduction in membrane localized E-cadherin in regenerating epithelium, even though E-cadherin mRNA was demonstrable in this population. In wounded confluent HT29 layers, migrating cells also showed reduced E-cadherin immunostaining. These data support the notion that the motility of restitutive epithelial cells may relate to altered patterns of E-cadherin and that this may play an important role in the reconstitution of epithelial integrity after mucosal injury.