Late human gestation is associated with an increase in the concentration of cortisol (F) in the fetal circulation and amniotic fluid. It had been assumed that most of the F measured in the amniotic fluid came from the fetal adrenal gland. However, local production of F can also occur in human intrauterine tissues from inactive cortisone under the influence of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1. Recent studies have shown that 11beta-HSD 1 activity is up-regulated by prostaglandins (PG) E2 and F2alpha, hormones that are produced in the fetal membranes (FM) at term. In the present study, we hypothesized that 11beta-HSD 1 expression would increase in FM during pregnancy and at labor, creating the potential for local increase in F production at term. We examined 11beta-HSD 1 expression in placenta and FM obtained during normal pregnancy from nonlaboring women [26-28 wk (n = 3); 29-30 wk (n = 3); 32-33 wk (n = 3); 35-36 wk (n = 3)] and from uncomplicated term pregnancies after elective cesarean section (n = 6). 11beta-HSD 1 expression was also examined in amnion and chorionic tissues in relation to term labor (n = 12). Immunohistochemistry and Western blot analysis were used to examine 11beta-HSD 1 localization and expression. 11beta-HSD 1 activity was also measured in microsomal fractions prepared from whole fetal membranes. At term, immunoreactive 11beta-HSD 1 expression was localized predominantly to the chorion trophoblast cells, attached decidua, and amnion epithelial cells. 11beta-HSD 1 expression in FM increased with gestational age and reflected increased enzyme reductase activity. No change in 11beta-HSD 1 expression was found in placental tissue from the same patients. There was a significant increase in 11beta-HSD 1 expression in amnion but not in chorion with the onset of labor. We suggest that increases in 11beta-HSD 1 expression/activity by intrauterine membranes during late gestation may result in increased potential for a local increase in F production and that FM should be considered as an extraadrenal source of F during late gestation. This local F production may be involved in different pathways contributing to the regulation of parturition.