CRF, a hypothalamic neurohormone, has been shown to be present in several tissues outside the brain. During pregnancy, both fetal (placental trophoblast, chorion, and amnion) and maternal (decidua) intrauterine tissues contain immunoreactive CRF. A paracrine/autocrine role of CRF as a regulator of hormonogenesis in human placenta and decidua has been suggested. The expression of CRF mRNA in human decidua was demonstrated in the present study by Northern blot analysis and was found to be higher in specimens collected at term than in those collected during the first and second trimesters of gestation. Furthermore, the presence of CRF was detected immunocytochemically in cultured decidual cells isolated from term decidua as well as in endometrial stromal cells decidualized in vitro by treatment with a mixture of medroxyprogesterone acetate, estradiol, and relaxin. These results indicate that human decidua is an intrauterine extrahypothalamic source of CRF in the maternal compartment and offer new tools to explore the in vitro decidualization processes and the regulation of CRF release from decidual cells.