Immunoreactive CRH (IrCRH) is produced locally in experimentally induced and spontaneous inflammation. Where it exerts autocrine or paracrine proinflammatory effects. In addition, CRH is secreted by the human placenta, rat Leydig cells, and rat and human ovaries, where it may participate in the inflammatory processes of ovulation and luteolysis, and/or the regulation of steroidogenesis. Finally, CRH is secreted in vitro by cultured human epithelial and decidualized stromal endometrial cells. To investigate the presence of CRH in human endometrium in vivo, we examined this tissue immunohistochemically and by extraction/RIA using a polyclonal, highly specific antirat/human CRH antibody. Endometrial biopsies from 33 women, aged 23-43 yr (median age, 33.5 yr), were performed by linear endometrial curettage for diagnostic purposes at different stages of the cycle. Intense IrCRH staining was localized in the cytoplasm of cells of the endometrial glands in all samples examined. IrCRH was also found in endometrial stromal cells exhibiting decidual reaction and in local immune accessory cells. The mobility of the endometrial IrCRH molecule was similar to that of r/hCRH in reverse phase high pressure liquid chromatography. The presence of CRH in the endometrium, and more specifically in the glandular epithelium during the proliferative and secretory phases of the menstrual cycle together with its known proinflammatory properties, suggest that this neuropeptide might participate in the inflammatory-like phenomena of endometrial physiology, such as menstrual shedding, surface epithelium repair, and/or implantation of the blastocyst. The presence of CRH in decidualized stromal cells is in accordance with its previously reported production by in vitro decidualized cultured endometrial stromal cells as well as by the placental decidua.