The purpose of this project is to understand better the development of the endometrium and oocyte in women and to investigate the role of gonadal steroids in these processes and in the pathophysiology of endometriosis and leiomyomata. Efforts during this reporting period characterized the temporal localization of estrogen receptosr (ER) alpha and beta in the endometrium and endometrial explants of women with endometriosis throughout the menstrual cycle. Samples were obtained during laparoscopic laser excision of lesions. Histological dating was performed using the criteria of Noyes. Immunohistochemical staining was carried out using antibodies directed against ER alpha and ER beta. ERa had a nuclear localization that was greatest in the epithelium during the proliferative phase and decreased during the late secretory phase. ERbeta showed a similar nuclear and epithelial cell preference but the intensity of ER beta immunostaining was increased during the secretory phase. Endometriosis explants showed higher ER beta staining than the corresponding endometrium obtained at the same time of the cycle. These different patterns of staining during the menstrual cycle with nuclear down regulation of ER alpha and upregulation of ER beta in the glandular epithelium during the secretory phase suggest differential regulation, and possibly roles, of the two receptors in the endometrium. The up-regulation of ER beta in endometriosis may provide a clue to therapy.