The expression pattern of two Ca2(+)-dependent intercellular adhesion molecules, E- and P-cadherin, in 54 surgically resected gastric adenocarcinomas was examined immunohistochemically. E-cadherin was expressed uniformly at the cell-cell borders of most of the differentiated and adherent-type undifferentiated gastric adenocarcinomas, showing that E-cadherin serves as the main cadherin molecule responsible for intercellular binding in these carcinomas. Scattered-type undifferentiated gastric adenocarcinomas which apparently lacked this tight intercellular adhesion were divisible into two groups on the basis of E-cadherin expression. In a minor group composed of 4 carcinomas, E-cadherin could not be detected, suggesting that the absence of E-cadherin made the cancer cells separate. In contrast, cancer cells of 19 carcinomas which belonged to the major group showed similar scattering but had definite expression of E-cadherin on their cell surfaces, suggesting that there was some mechanism(s) disturbing the function of E-cadherin in these carcinomas. However, immunoblotting showed no evidence of gross alterations of the E-cadherin molecule, such as partial deletion, in these carcinomas. P-cadherin was expressed in 29 (54%) of the examined gastric carcinomas, and the expression was unstable in most of them, a characteristic feature compared with the stable expression of E-cadherin. Since P-cadherin is known to be expressed temporarily in the foregut during embryogenesis and was proved to be occasionally expressed, although weakly, in the proliferative zone of noncancerous gastric epithelia in this study, expression of P-cadherin in gastric carcinomas may be an oncofetal phenomenon and/or may reflect their marked proliferative potential.