In pathological pregnancies, alterations in circulating maternal and fetal adrenomedullin (ADM) concentrations may mediate compensatory vascular responses in the fetal or placental circulation. To address whether ADM is a potential paracrine vasoactive factor within the placenta, the regional distribution and cellular localization of ADM mRNA expression were determined by Northern blot and in situ hybridization of different regions of the placenta and fetal membranes from pregnancies complicated by severe preeclampsia [<28 wk (n = 7) and >28 wk (n = 13)] and from normotensive pregnancies [<28 wk (n = 6) and >28 wk (n = 15)]. Northern blotting revealed that ADM mRNA (1.3 kb) was expressed in chorionic villi and basal plate regions, but was most abundantly expressed in the choriodecidua. By in situ hybridization, ADM mRNA was localized to the syncytiotrophoblasts and the extravillous cytotrophoblasts in the basal plate and choriodecidua regions. ADM mRNA expression was increased in the choriodecidua, syncytial knots, and cytotrophoblasts in peri-infarct regions in preeclampsia. In chorionic villous explant studies maintained at reduced oxygen tension, ADM mRNA abundance was increased at 12, 24, and 48 h. ADM mRNA expressed in syncytiotrophoblasts and cytotrophoblasts in the basal plate decidua and choriodecidua may contribute to the maternal and fetal plasma levels. In preeclampsia, regional increases in ADM mRNA may be induced by hypoxia and mediate local fetal/placental adaptive responses to reduced placental perfusion.