BACKGROUND: Morbidity and mortality rates from acute respiratory failure remain noteworthy despite advances in conventional ventilatory techniques and improvements in supportive care. Repeated, the large tidal volume breaths during positive pressure mechanical ventilation lead to destruction of alveoli and pulmonary capillaries. Moreover, the overdistention of terminal lung units is considered as an important mechanism of ventilator induced lung injury. High frequency ventilation (HFV) is a technique involving a small tidal volume, and a higher than physiologic respiratory rate. Partial liquid ventilation (PLV), also known as perfluorocarbon-associated gas exchange, is a new technique for respiratory support. This study was designed to compare conventional mechanical ventilation (CMV) and high frequency jet ventilation (HFJV), in combination with PLV. METHODS: Twenty rabbits were anesthetized with xylazine, ketamine and vecuronium. We studied rabbits with lung injury induced by saline lavage. Animal were randomized into one of two treatment groups. Ventilator parameters included the following; CMV: FIO2 of 1.0, respiratory rate 20-30 breaths/min, I/E ratio 1 : 1; HFJV: respiratory rate 2 Hz, driving pressure 2psi. Animals were briefly disconnected from the ventilator and lungs were lavaged with warmed saline. This procedure was repeated until PaO2 < 100 mmHg. After one hour, we initiated the instillation of perfluorodecalin via an endotracheal tube. Baseline measurements were performed at 60 mins after the induction of anesthesia and repeated again at hour after the induction of lung injury, which included 30 mins of stabilization. After PFD instillation, data were recorded. RESULTS: All animals developed hypoxemia after the lung injury, but oxygenation improved significantly after perfluorodecalin instillation. The PLV-HFJV group showed a high pH and a low PaCO2. Mean arterial pressure, cardiac index and systemic vascular resistance was differed significantly. Although there were no qualitative histological differences between lungs ventilated with HFJV on CMV, the lower lobes of all PLV-treated animals were damaged less than the upper lobes, but without statical significance. CONCLUSIONS: PLV-HFJV produced a more efficient gas exchange than PLV-CMV. No significant difference was observed in the pulmonary pathologies of the groups.