In mineralocorticoid target organs, 11β-hydroxysteroid dehydrogenase type II (11β-HSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive metabolites. Placental 11β-HSD2 is also thought to protect the fetus from high levels of circulating maternal glucocorticoid. In this study, we examined the immunoreactivity of 11β-HSD2 and MR in human placenta from 5 weeks gestation to full term using immunohistochemistry, 11β-HSD2 messenger RNA (mRNA) expression using Northern blot analysis, and MR mRNA expression using RT-PCR analysis. Marked 11β-HSD2 immunoreactivity was detected in placental syncytiotrophoblasts at all gestational stages. MR immunoreactivity was moderately detected in syncytiotrophoblasts, some cytotrophoblasts, and interstitial cells of the villous core. Marked mRNA expression of 11β-HSD2 was detected in placenta by Northern analysis. RT-PCR analysis of MR in placental tissues showed an amplified product consistent in length with the primers selected. These results suggest that placental 11β-HSD2 is involved in not only regulating the passage of maternal active glucocorticoids into the fetal circulation but also in regulation of maternal-fetal electrolyte and water transport in the placenta, as in other mineralocorticoid target organs.