The effect of hyperosmolar fluid aspiration (seawater) on lung fluid balance has not been well studied. Therefore, the effect of this clinically relevant form of acute lung injury on the alveolar epithelial and lung endothelial barriers was examined in ventilated, anesthetized rabbits. Seawater (4 ml/kg body weight, 881 +/- 29 mOsm/kg) with 3 microCi of 125I-albumin was instilled into the lower trachea of ventilated, anesthetized rabbits. Osmotic equilibration with plasma was completed within the first 5 min after seawater instillation. In parallel with the osmotic equilibration of the seawater in the air spaces, there was a 3-fold dilution of the alveolar protein tracer 125I-albumin, indicating an initial large (300%) increase in alveolar fluid volume. There was a marked decline in arterial oxygenation at the same time that the alveolar fluid volume markedly increased. The initial dilution of the alveolar protein tracer was followed by a progressive increase in the alveolar protein tracer concentration that continued until 6 h after seawater instillation. As the alveolar protein tracer concentrated, arterial oxygenation improved, indicting net alveolar liquid clearance. There was only a mild increase in the epithelial and endothelial permeability to protein within the first 2 h after seawater instillation. Thus, a large osmotically induced increase in alveolar fluid volume with severe pulmonary edema did not cause sustained injury to the endothelial or epithelial barriers of the lung. In fact, normal alveolar liquid clearance occurred, indicating the resistance of the epithelial barrier to hyperosmolar injury as well as its capacity to rapidly reabsorb excess alveolar fluid.