Objective: To test the hypothesis that treatment with vaporized perfluorocarbon affects the relative pulmonary blood flow distribution in an animal model of surfactant-depleted acute lung injury. Design: Prospective, randomized, controlled trial. Setting: A university research laboratory. Subjects: Fourteen New Zealand White rabbits (weighing 3.0-kg). Interventions: The animals were ventilated with an F10(2) of 1.0 before induction of acute lung injury. Acute lung injury was induced by repeated saline lung lavages. Eight rabbits were randomized to 60 mins of treatment with an inspiratory perfluorohexane vapor concentration of 0.2 in oxygen. To compensate for the reduced F10(2) during perfluorohexane treatment F10(2) was reduced to 0.8 in control animals. Change in relative pulmonary blood flow distribution was assessed by using fluorescent-labeled microspheres. Measurements and Main Results: Microsphere data showed a redistribution of relative pulmonary blood flow attributable to depletion of surfactant. Relative pulmonary blood flow shifted from areas that were initially high-flow to areas that were initially low-flow. During the study period, relative pulmonary blood flow of high-flow areas decreased further in the control group, whereas it increased in the treatment group. This difference was statistically significant between the groups (p =.02) as well as in the treatment group compared with the initial injury (p =.03). Shunt increased in both groups over time (control group, 30% +/- 10% to 63% +/- 20%; treatment group, 37% +/- 20% to 49% +/- 23%), but the changes compared with injury were significantly less in the treatment group (p =.03). Conclusion: Short treatment with perfluorohexane vapor partially reversed the shift of relative pulmonary blood flow from high-flow to low-flow areas attributable to surfactant depletion.