Perfluorocarbons accumulate in the dependent regions of the lungs, which may result in regional hypoxia if ventilation with oxygen is insufficient to oxygenate the dependent perfluorocarbon-filled alveoli. In this issue of Critical Care, Max et al present data that demonstrate a decrease in arterial oxygen tension (PaO2) at 30 min compared to that observed at 5 min after administration of FC 3280. These data suggest failure of on-going ventilation/oxygenation to support the initial increase in PaO2 attributed to the oxygen dissolved in the administered perfluorocarbon. Studies such as this one demonstrate that development of the optimal partial liquid ventilation (PLV) technique is ongoing.