Epithelial cells of human endometrium and differentiated endometrial stromal cells express the corticotropin-releasing hormone (CRH) gene. CRH is also produced by the human placental cytotrophoblast. Endometrial and placental CRH is under the endocrine control of gonadal steroids as well as under an autocrine/paracrine regulation by prostanoids and interleukins. Human endometrium, myometrium and placenta also express the relevant receptors. Invasive trophoblasts promote apoptosis of activated Fas-expressing human T lymphocytes, an effect potentiated by CRH and inhibited by the CRH type 1 antagonist, antalarmin. Female rats treated with antalarmin during the first 6 days of gestation had a dose-dependent decrease of implantation sites and live embryos, and significantly decreased endometrial FasL expression. Our data suggest important physiological roles of endometrial and placental CRH in the regulation of decidualization, blastocyst implantation, and early maternal tolerance.