The expression of P-cadherin, one of the Ca(2+)-dependent cell-cell adhesion molecules, in human gastric carcinomas was examined by Northern blotting, Western blotting and immunohistochemistry. P-cadherin mRNA was expressed in all the gastric carcinoma tissues examined, whereas no message was detected in non-neoplastic mucosa. By Western-blot analysis, P-cadherin protein was expressed in 83% and 29% of the well-differentiated and poorly differentiated gastric adenocarcinomas, respectively, the incidence being significantly different. Immunohistochemically, P-cadherin immunoreactivity was localized on the cell surface or the cell-to-cell borders of well-differentiated adenocarcinomas. P-cadherin was not detected in Borrmann's type-4 or scirrhous carcinomas where the tumor cells proliferate diffusely with productive fibrosis. The level of P-cadherin expression in stage-2 carcinomas was significantly higher than in stage-I carcinomas. In the case of patients in stages 2 to 4, however, the level of P-cadherin expression decreased as the stage progressed, the difference between stages 2 and 3 and between stages 3 and 4 being significant. Our findings suggest that P-cadherin might play an important role in the development of well-differentiated gastric adenocarcinomas and the decreased expression of P-cadherin might be responsible for the infiltrative growth and progression of gastric carcinomas.