At birth, fetal distal lung epithelial (FDLE) cells switch from active chloride secretion to active sodium (Na⁺) reabsorption. Sodium ions Senter the FDLE and alveolar type II (ATII) cells mainly through apical nonselective cation and Na⁺-selective channels, with conductances of 4–26 pS (picoSiemens) in FDLE and 20–25 pS in ATII cells. All these channels are inhibited by amiloride with a 50% inhibitory concentration of <1 μM, and some are also inhibited by [N-ethyl-N-isopropyl]-2′-4′-amiloride (50% inhibitory concentration of <1 μM). Both FDLE and ATII cells contain the α-, β-, and γ-rENaC (rat epithelial Na⁺ channels) mRNAs; reconstitution of an ATII cell Na⁺-channel protein into lipid bilayers revealed the presence of 25-pS Na⁺ single channels, inhibited by amiloride and [N-ethyl-N-isopropyl]-2′-4′-amiloride. A variety of agents, including cAMP, oxygen, glucocorticoids, and in some cases Ca²⁺, increased the activity and/or rENaC mRNA levels. The phenotypic properties of these channels differ from those observed in other Na⁺-absorbing epithelia. Pharmacological blockade of alveolar Na⁺ transport in vivo, as well as experiments with newborn α-rENaC knock-out mice, demonstrate the importance of active Na⁺ transport in the reabsorption of fluid from the fetal lung and in reabsorbing alveolar fluid in the injured adult lung. Indeed, in a number of inflammatory diseases, increased production of reactive oxygen-nitrogen intermediates, such as peroxynitrite (ONOO⁻), may damage ATII and FDLE Na⁺ channels, decrease Na⁺ reabsorption in vivo, and thus contribute to the formation of alveolar edema.