Objectives: To investigate the changes In pulmonary function and gas exchange during application of 18% perfluorohexane vapor in healthy and in olelc acid-injured animals and compare It with an Injured control group. Design: Prospective randomized controlled study. Setting. Experimental research laboratory at a university medical center. Subjects: Nineteen sheep weighing 31.4 +/- 4.1 kg. Interventions: Lung injury was Induced In 14 sheep by the intravenous injection of 0.1 mL/kg olelc acid. After establishment of lung injury (Pao(2)/Fio(2) ratio, <200; pulmonary artery occlusion pressure, <19 torr), seven animals were treated with 18% perfluorohexane vapor for 30 mins whereas seven animals served as controls. After the start of perfluorohexane treatment, blood gases and respiratory and hemodynamic data were collected in 10-min intervals throughout the study period of 1 hr. In addition, five healthy animals received perfluorohexane vapor for 30 mins and were followed up for 2 hrs to exclude delayed negative effects. Measurements and Main Results: Treatment of healthy animals with 18% perfluorohexane vapor was not accompanied by any significant adverse effects. It was associated with a significant decrease of alveolar-artetial oxygen difference during perfluorohexane application (p <.05). In Injured animals, 18% perfluorohexane led to a sustained improvement of peak inspiratory pressures within 10 mins of treatment (p <.001). The concomitant Increase In compliance was equally significant (p <.001). Significant Improvements In Pao(2) occurred despite a decrease In Fio(2) to 0.81 at the end of vaporization. Conclusion: Healthy animals tolerated perfluorohexane vapor well without significant changes In oxygenation and mechanical lung function for 2 hrs. In injured animals, application of perfluorohexane vapor primarily Improved peak Inspiratory pressure and compliance. The Increase of oxygenation therefore could be secondary to an improvement In compliance.