To study the effects of subacute hypoxia on alveolar epithelial ion transport, alveolar fluid clearance was measured in isolated fluid-filled rat lungs. After instillation of a solution containing about 5% bovine albumin, an increase in alveolar fluid clearance was measured over 2 hours. Alveolar fluid clearance was lower when rats were kept in hypoxic conditions (FiO2 = 0.1) for 48 hours. Neither 10(-5) M amiloride (a Na(+)-channel blocker) nor 10(-3) M ouabain (an inhibitor of Na(+)-K(+)-ATPase) inhibited fluid clearance in the hypoxia group, but they did in the normoxia group. These results indicate that subacute hypoxia may down-regulate both the Na(+)-channl and Na(+)-K(+)-ATPase, and thus decrease the absorption of excess alveolar fluid.