Syndecans, cell surface heparan sulphate proteoglycans, are known to function as cell adhesion molecules and as a co-receptor for heparin-binding growth factors that have important roles in tissue homeostasis and repair, but the localization of syndecans in gastric mucosa and their role in gastric ulcer healing are not known. The licalization of syndecan-1, a subfamily protein of syndecans expressed on epithelial cells, was studied in 12 surgically resected human stomachs containing an ulcer or early scar tissue. Localization of syndecan-1 was detected both by immunohistochemistry and by in situ hybridization In non-ulcer sites of gastric mucosa, syndecan-1 protein was expressed at the basolateral surface of foveolar epithelial cells and the cells of intestinal metaplasia, and at the cell surface of stromal plasma cells. In addition, positive dots of syndecan-1 were found in the cytoplasmic area of parietal cells. Foveolar epithelial cells at active stage ulcer margins showed nearly the same intensity of staining as those at non-ulcer site mucosa. By contrast, enhanced staining was obtained in elongated regenerative foveolar cells at the healing ulcer margins and the early scar tissues. The migrating cells on ulcer floors also expressed syndecan-1 protein. The expression sites of syndecan-1 mRNA mostly coincided with those of syndecan-1 protein. These results suggest that syndecan-1 participates in cell adhesion mainly at the foveolar epithelium and plays a role in the healing of gastric ulcers by interacting with heparin-binding growth factors.