Alveolar epithelial cells of mammalian lungs actively transport sodium (Na+) and chloride (Cl-) ions and these processes are important in fluid homeostasis. Sodium ions enter the apical membranes of both type I and type II alveolar epithelial cells through sodium selective, cation and cyclic nucleotide gated ion channels and are extruded across the basolateral membrane by the ouabain-sensitive Na,K-ATPase. This vectorial transport of Na+ ions (and concomitant movement of Cl- ions to maintain electroneutrality) creates an oncotic force leading to the reabsorption of fluid across both normal and damaged lungs. Nitric oxide and reactive oxygen nitrogen intermediates (formed by the reactions of nitric oxide with partially reduced oxygen species), generated in close proximity of epithelial cell membranes by activated inflammatory cells, modulate the activity of sodium channels via signal transduction mechanisms (such as increasing PKG and PKC) or by post-translational oxidative modifications of sodium channel proteins and their chaperons. Channel activity (and vectorial sodium transport) may be either increased or decreased depending on levels of reactive intermediates and length of exposure. Better understanding of these interactions would offer considerable new insights into the mechanisms leading to pulmonary edema in a number of pathological conditions. © 2008 Elsevier Inc. All rights reserved.