Two infants on high-frequency oscillatory ventilation for chronic lung disease and severe respiratory failure, received a bolus of warmed and oxygenated perfluorodecalin up to residual functional capacity, followed by a continuous infusion of 6 ml/kg/hour. Our aim was to improve gas exchange without increasing ventilatory-induced lung injury. Heart rate, oxygen saturation, blood pressure, and TcPO2/TcPCO2 were continuously monitored during treatment. Arterial blood gas was evaluated every 3 hours. Both patients showed improvement of gas exchange with a 13.6 and 12.5% reduction of oxygenation index, respectively. High-frequency partial liquid ventilation is an experimental ventilation technique that could be considered as rescue treatment, to improve oxygenation in subjects with critical respiratory failure. This method could probably produce less damage, than other ventilation modes, to severely injured lungs.