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Unlabelled: Perflurocarbons (PFCs) are used during liquid ventilation and as hemoglobin substitutes. PFCs reduce free radical generation and damage to the lung during liquid ventilation. Thus, we examined the effects of parenteral administration of PFCs on lung injury after acid aspiration. Rats were treated with intraperitoneal injection of either FC-77 or IV injection of Fluosol. Controls received intraperitoneal or IV normal saline (NS) before or at the time of injury and then were injured by instillation of NS + HCl (pH = 1.25) into their lungs via a tracheotomy. The animals were exposed to air or 98% oxygen, breathing spontaneously. The rats were injected with 0.05 microCi of (125)I-albumin (bovine serum albumin) before injury. The extent of lung injury was assessed 5 h postinjury by compliance and lung albumin permeability index measurement. Myeloperoxidase (MPO) activity and histologic examination were used to assess neutrophilic infiltration. Both FC-77 and Fluosol decreased the permeability index compared with controls (1.05 +/- 0.08; 1.08 +/- 0. 12, respectively, versus 1.34 +/- 0.21) and improved lung compliance after intratracheal instillation of 1.2 mL/kg of HCl/NS, pH = 1.25 + hyperoxia injury (P < 0.05). Lung MPO activity decreased in the FC-77 group and was associated with a concomitant decrease in neutrophil infiltration. MPO activity of the spleen increased after FC-77 treatment. The administration of FC-77 decreased the severity of lung permeability changes associated with acid in the presence or absence of hyperoxia exposure. These data suggest that attenuation of neutrophilic infiltration by PFCs decreases lung injury., Implications: Intraperitoneally administered perfluorocarbons in rats attenuate the neutrophilic infiltration in the lung after acid aspiration, thereby decreasing the alveolar protein leakage and improving pulmonary compliance.