The transition of the epithelium of the fetal lung from fluid secretion to fluid reabsorption requires changes in the expression of ion channels. Corticosteroids regulate expression of several of these channels, including the epithelium sodium channel (ENaC) subunits and aquaporins (AQP). We investigated the ontogenetic changes in these ion channels in the ovine fetal lung during the last half of gestation, a time of increasing adrenal maturation. Expression of the mRNAs for the chloride channels, cystic fibrosis transmembrane conductance regulator (CFTR) and chloride channel 2 (CLCN2) decreased with age. Expression of mRNAs for AQP1, AQP5, and for subunits of ENaC (, , ) increased with age. In the fetal sheep the expression of ENaC mRNA was dramatically higher than the expression of ENaC or ENaC, but expression of ENaC protein decreased with maturation, although the ratio of the mature (112kD) to immature (102kD) ENaC protein increased with age, particularly in the membrane fraction. In contrast, ENaC mRNA and protein both increase with maturation, and the mature form of ENaC (68kD) predominates at all ages. A modest increase in fetal cortisol, within the range expected to occur naturally in late gestation but prior to active labor, increased ENaC mRNA but not ENaC, ENaC or AQP mRNAs. We conclude that in the ovine fetal lung appearance of functional sodium channels is associated with induction of ENAC and ENaC, and that ENaC expression may be induced by even small, preterm increases in fetal cortisol.