Ovarian surface epithelium (OSE), the source of common epithelial carcinomas, is a simple mesothelium that during carcinogenesis acquires complex epithelial characteristics normally found in tubal, endometrial, and endocervical epithelia. These characteristics include the intercellular adhesive molecule E-cadherin. We examined cryostat sections of 12 normal ovaries by immunofluorescence and immunocytochemistry to determine whether E-cadherin is a component of normal OSE that is retained in ovarian cancers or whether it, like many other epithelial characteristics, is acquired in the course of metaplasia and neoplastic progression. E-cadherin expression by OSE varied with its location within the ovary and with cell shape. It was present inconsistently on the ovarian surface but was increased in surface invaginations and particularly in epithelial inclusion cysts. Independent of location, E-cadherin was most prominent in columnar, variable in cuboidal, and absent in flat OSE. This relationship to cell morphology accounts for the increased E-cadherin expression in inclusion cysts, which are sites of frequent metaplastic and dysplastic changes. These results suggest that the morphologic variation of OSE reflects differences in E-cadherin-mediated intercellular adhesion. Thus, the appearance of this adhesion molecule in columnar OSE may represent an early step in the increased commitment to epithelial phenotypes that accompanies metaplasia and neoplastic progression of OSE.