Corticotrophin releasing hormone (CRH), is produced by the human placenta, fetal membranes and decidua and has been detected in maternal and fetal plasma and amniotic fluid during human pregnancy. Previous studies of the cellular localization of CRH in the placenta and fetal membranes have yielded conflicting results. In this study, placentae were obtained from uncomplicated pregnancies immediately after elective termination or after normal delivery at term. Zamboni's fixed sections of villi and membrane-decidua, were cut at 10 microns by cryostat and immunocytochemistry was performed using an anti-rat/human CRH antiserum. In first and second trimester placentae, the amount of CRH reaction product present was variable. CRH was localized in both the syncytiotrophoblast and cytotrophoblast in first and second trimester tissue. In term placentae, CRH was identified consistently in the syncytiotrophoblast. In addition, strong CRH reaction was localized to the amnion epithelium of the fetal membranes. Positive immunoreactivity was also detected in the chorion and decidua although at a lower level of intensity. In trophoblast cells and in the amnion epithelium, CRH reaction product was contained in distinct granules. The regulation of CRH and its physiological role may differ in these diverse cell types. Possible effects of CRH include autocrine or paracrine actions within the amnion, chorion and decidua while CRH derived from syncytiotrophoblast may have endocrine effects through access to the maternal and fetal circulations.