Endothelin (ET-1) is thought to play an important role in the regulation of pulmonary vascular tone, alveolar fluid balance and hypoxia-induced pulmonary edema. ET-1 antagonists counteract the pulmonary vascular permeability and hypertension; but effects on alveolar fluid reabsorption are not understood. This study was undertaken to clarify the effect of ET-1 on lung alveolar Na- and fluid-reabsorption. Reabsorption was measured in fluid instilled rat lungs with and without with ET-1 [10-7 M] and amiloride [100 mM] in normoxia. Reabsorption was measured with albumin as a marker of volume changes. Effects of ET-1 on transepithelial transport of cultured primary rat alveolar epithelial type II cells were measured as the short circuit current (ISC) in Ussing chambers. Fluid reabsorption was ~20% per 30 min in controls. ET-1 reduced the reabsorption by ~60%. In the presence of amiloride the reabsorption was reduced further both in the ET-1 and control rat lungs to equal values, indicating that ET-1 decreases amiloride-sensitive Na-transport. In Ussing chambers, addition of ET-1 in different doses to the apical and/or basolateral side had no effect on the ISC and its amiloride sensitive component. These findings indicate that ET-1 reduces fluid reabsorption in rat lungs, but has no direct effect on the epithelial Na transport in alveolar type II cells. It might act through indirect mechanisms on epithelial Na channels which require the epithelial barrier to be intact.