Addition of ionic and nonionic water-soluble polymers to pulmonary surfactants in the presence of inactivating substances prevents surfactant inactivation in vitro and improves lung function in several models of lung injury. However, a recent report found opposite effects when surfactant plus polyethylene glycol (PEG) was used to treat lung injury caused by saline lung lavage. Therefore, we examined the reasons why the polymer effect is less evident in the saline lung lavage lung injury model. We treated rats with lavage lung injury with a commercial lung surfactant extract derived from bovine lung (Survanta) with or without addition of PEG. Groups treated with Survanta + PEG had significantly higher static post mortem lung volumes than groups treated with Survanta. However, groups treated with Survanta + PEG had more tracheal fluid and no significant benefit in arterial oxygenation compared with the group treated with Survanta, despite our use of measures to reduce pulmonary edema. Measurements after intravascular injections of 125I-labeled albumin confirmed that addition of PEG increased extravascular lung water and that this effect is mitigated by furosemide. We conclude that surfactant + PEG mixtures are less effective in lavage injury than in other forms of lung injury because of increased extravascular lung water. Copyright © 2005 International Pediatric Research Foundation, Inc.