Hypoxia increases filtration of fluid into the alveolar space. Its removal is driven by active Na transport across the alveolar wall. Hypoxia also inhibits alveolar Na- and water reabsorption. Gluco-corticoids are known to stimulate alveolar Na and water reab-sorption in normoxia; effects in hypoxia are not known. To test whether dexamethasone might prevent the inhibition of alveolar reabsorption in hypoxia, rats were treated with dexamethasone (DEX; 2mg/kg/day i.p.) on three consecutive days. On days 2 and 3 rats were also exposed to hypoxia (10% O2). Fluid reabsorption was measured in trapanal-anaesthesia after instillation of 3ml medium (± amiloride; 100mM) containing albumin as a volume marker. mRNA expression of Na transporters in lung tissue was measured by RT-PCR. In normoxia DEX caused a 2-fold increase in alveolar fluid clearance. Hypoxia caused inhibition in control and DEX-treated rats, but DEX brings reabsorption back to normal. All effects can be explained by changes in the amiloride-sensitive component of reabsorption. DEX increased the mRNA of a and [gamma] ENaC. These results indicate that the prophylactic treatment with DEX increases alveolar fluid clearance by stimulation of ENaC expression and prevents the transport inhibition in hypoxia.