We sought to know whether there is a further improvement in gas exchange when partial liquid ventilation (PLV) is added to high-frequency oscillatory ventilation (HFOV) in a piglet model of saline lavage-induced acute lung injury. Seven 7-9 day-old newborn piglets of mixed strain were treated with repeated saline lavage to achieve a uniform degree of acute lung injury. Then, HFOV were applied to the subject. Four animals received two consecutive doses (15 mL/kg) of perfluorodecalin at 30-min interval (PFC+HFOV group). The other three animals remained on HFOV alone (HFOV-only group). Repetitive lung lavage led to a significant acute aggravation in both gas exchange and hemodynamic parameters. Subsequent application of HFOV produced a significant rapid recovery in both gas exchange and hemodynamic parameters to near baseline levels. During and after perfluorodecalin dosing, there were no significant changes in gas exchange or hemodynamic parameters over time in both groups, and no significant differences in gas exchange or hemodynamic parameters between groups. We concluded that the addition of 30 mL/kg of perfluorodecalin to HFOV showed no detrimental effect on hemodynamics, but did not produce a significant improvement in gas exchange over a three-hour period.