We hypothesized that apneic oxygenation, using an open lung approach, combined with extracorporeal CO2 removal, would provide adequate gas exchange in acute lung injury. We tested this hypothesis in nine anesthetized and mechanically ventilated pigs (85-95 kg), in which surfactant was depleted from the lungs by repeated lung lavage. After a lung recruitment maneuver, the tracheal tube was connected to 20 cm H2O continuous pressure (100% O2) for oxygenation of the blood. A pumpless membrane ventilator (interventional lung assist by Novalung) was connected in an arteriovenous shunt for CO2 removal. PaO2 and PaCO2 were recorded for 3.5 hours. PaO2 was 464 (403, 502) mm Hg (median and interquartile range) throughout the experiment. The O2 uptake through the lungs was 185 (164, 212) ml/min. PaCO2 increased asymptotic towards 60 mm Hg. The CO2 removal through the membrane ventilator was 180 (150, 180) ml/min. Thus, the method provided adequate gas exchange in this experimental model, suggesting that it might have potential as an alternative treatment modality in acute lung injury.