The purpose of this study was to investigate the influence of different inhaled perfluorocarbons (PFC) upon pulmonary mechanics and gas exchange in a saline lavage model of acute lung injury. A randomized, controlled animal trial was conducted at the university hospital laboratory. Pulmonary gas exchange (pGE), static compliance (Cst), and basic hemodynamics (heart rate [HR], arterial [AP] and central venous pressures [CVP]) were compared. After induction of lung injury by repeated pulmonary lavage with saline solution, 35 New Zealand rabbits (3 +/- 0.2 kg) were randomized into five groups with seven animals each: 1) conventional ventilated control, 2) perfluorooctane (octane), 3) Perflubron (perfluorooctylbromide [PFOB]), 4) Perfluoro-1,3,5-trimethylcyclohexane (PP 4), and 5) perfluorohexane (hexane). Consecutively, PFC groups were subjected to a 120 minute study period applying mechanical ventilation (tidal volume of 7 ml/kg) in conjunction with PFC performed by a modified halothane vaporizer. Amount of vaporization was controlled by weighing the vaporizer at approximately 25 ml/h/kg body-weight PFC. Controls remained gas ventilated. After injury, PaO2 was control = 53 +/- 13 mbar, octane = 55 +/- 24 mbar, perflubron = 57 +/- 18 mbar, PP4 = 68 +/- 25 mbar, and hexane = 51 +/- 16 mbar. Within the 120 minute period, PaO2 was control = 51 +/- 19 mbar, octane = 42 +/- 6 mbar, perflubron = 40 +/- 11 mbar, PP4 = 47 +/- 10 mbar, and hexane = 60 +/- 8 mbar, respectively. At baseline, after injury, and throughout the study period, pGE and Cst, as well as HR, AP, and CVP, did not significantly differ when compared with octane, PP4, PFOB, and controls (p > 0.05), whereas hexane significantly improved pGE and Cst (p < 0.05). From four different inhaled perfluorocarbons, only perfluorohexane has measureable impact upon gas exchange and lung mechanics when compared with a conventional lung protective ventilation mode.