Objective: To determine the spatial distribution of pulmonary blood flow in three groups of piglets: partial liquid Ventilation in normal piglets, partial liquid ventilation during acute lung injury, and conventional gas ventilation during acute lung injury. Design: Prospective randomized study.Setting: A university medical school laboratory approved for animal research. Subjects: Neonatal piglets.Interventions: Regional pulmonary blood flaw was studied in 21 piglets in the supine position randomized to three different groups: a normal group that received partial liquid ventilation (Normal-PLV) and two acute lung injury groups that received an oleic acid-induced lung injury: partial liquid ventilation during acute lung injury (OA-PLV) and conventional gas ventilation during acute lung injury (OA-Control). Acute lung injury was induced by infusing oleic acid (0.15 mL/kg iv) over 30 mins. Partial liquid ventilation was instituted with perflubron (LiquiVent, 30 mL/kg) after 30 mins in the Normal-PLV and OA-PLV groups. Measurements and Main Results: Arterial and venous blood gases, hemodynamics, and pulmonary mechanics were measured every 15 mins throughout the hour-long study. Pulmonary blood flow was assessed by fluorescent microsphere technique at baseline and after 30, 45, and 60 mins. In the Normal-PLV piglets, pulmonary blood flow decreased from baseline (before injury or partial liquid ventilation) in the most dependent areas of the lung (F ratio = 3.227; p < .001). In the OA-PLV piglets, pulmonary blood flow was preserved over time throughout the lung (F ratio = 1.079; p = .38). In the OW-Control piglets, pulmonary blood flow decreased in the most dependent areas of the lung and increased from baseline in less dependent slices over time (F ratio = 2.48; p = .003). Conclusions: The spatial distribution of regional pulmonary blood flow is preserved during partial liquid ventilation compared with gas ventilation in oleic acid-induced lung injury.