Intrapulmonary administration of perfluorochemicals (PFC) has been suggested for reasons other than respiratory insufficiency. PFC application has been described to affect cerebral Hb concentration, however, data for healthy lungs are missing. Newborn piglets were randomized into 3 groups (30-ml slow-filling, 10-ml slow-filling and 30-ml rapid-filling), orally intubated and mechanically ventilated. Partial liquid ventilation (PLV) was initiated by filling the lung with PF5080 (10 or 30 ml/kg) at a rate of 1.5 ml/min (slow filling) or within 45 s (rapid filling). Vital signs, blood gases, tidal volume (VT) and changes in the cerebral concentration of oxygenated hemoglobin (HbO2) and total Hb were determined for up to 20 min. Rapid administration of PFC caused an immediate drop in HbO2, PaO2 and VT. The concentration of oxygenated and total Hb increased thereafter and remained high. We found a slow increase in PaCO2, HbO2 and total Hb in the 30-ml slow-filling group, but almost no changes in the 10-ml slow filling group (except for a decrease in PaO2). According to our data, PLV with 10 ml/kg should be preferred since cerebral alterations are minimal. If complete filling of the lung is needed PFC should be administered slowly to minimize side effects.