Tenascin has been recently characterized as an extracellular matrix glycoprotein involved in tissue interactions during fetal development and oncogenesis. In order to study the possible involvement of tenascin in epithelial growth of the human endometrium, we evaluated the expression of tenascin in 84 cases of normal, hyperplastic, or neoplastic human edometrium. The specimens were obtained by curettage and/or biopsy and analyzed by immunohistochemistry utilizing a newly developed monoclonal antibody against human tenascin. Weak periglandular immunoreactivity was observed in 50% of proliferative phase, but not in secretory endometrium. Approximately 60% of endometrial hyperplasia specimens had weak periglandular tenascin immunoreactivity, but its distribution was irregular and not necessarily correlated with degree of cell atypia. Invasive endometrial carcinomas displayed intense and diffuse staining around the carcinoma cells, in addition to thin periglandular immunoreactivity similar to that seen in hyperplasia. The intensity of tenascin staining in endometrial carcinoma was not related to the degree of tumor differentiation. These results suggest that tenascin appears as a result of interactions between neoplastic epithelium and stroma in tumor development and that diffuse and intense staining could be a stromal marker for the invading capacity of human endometrial malignancies.