Amiloride-sensitive epithelial sodium channel ENaC is a major sodium channel in the lung facilitating fluid absorption. ENaC is composed of -, -, and -subunits and the -subunit is indispensable for ENaC function in the lung. In human lungs, the -subunit is expressed as various splice variants. Among them, 1 and 2 are two major variants with different upstream regulatory sequences, and possessing similar channel characteristics when tested in Xenopus oocytes. Despite the importance of -ENaC, little was known about the relative abundance of its variants in lung epithelial cells. Furthermore, lung infection and inflammation are often accompanied by reduced -ENaC expression, oxidative stress, and pulmonary edema. However, it was not clear how oxidative stress affects expression of -ENaC variants. In this study, we examined relative expression levels of -subunit variants in four human lung epithelial cell lines. We also tested the hypothesis that oxidative stress inhibits -ENaC expression. Our results show that both 1 and 2 variants are expressed in the cells we tested but relative abundance varies. In the two monolayer-forming cell lines, H441 and Calu-3, 2 is the predominant variant. We also show that H₂O₂ specifically suppresses 1 and 2 variant expression in H441 and Calu-3 cells in a dose-dependent fashion. This suppression is achieved by inhibition of their promoters and is attenuated by dexamethasone. These data demonstrate the importance of the 2 subunit variant and suggest that glucocorticoids and antioxidants may be useful in correcting infection/inflammation-induced lung fluid imbalance.