We investigated the efficacy of intratracheal perfluorocarbon (PFC) administration combined with mechanical ventilation to support gas exchange in adult animals with acute respiratory failure. These were compared with a similar group of animals treated with continuous positive-pressure ventilation (CPPV) with respect to respiratory parameters and postmortem lung histology. After lung lavage with saline, 18 adult rabbits were divided into three groups (n = 6 per group). All groups received conventional CPPV Additionally, one group received intratracheal PFC administration at a volume of 18 ml/kg (corresponding to functional residual capacity) (PFC group); another received 18 ml/kg of saline administration (saline group), and the last had no further treatment (CPPV group). All groups were ventilated for 3 h using 100% oxygen, with the same ventilator settings of tidal volume of 12 ml/kg, respiratory frequency of 30/min, and positive end-expiratory pressure of 6 cm H2O. In the PFC group, Pa(O2) increased from 67.2 +/- 11.4 to 424.2 +/- 14 mm Hg and remained stable for 3 h with well-preserved Pa(CO2) values. Only in the PFC group were significant decreases in airway pressures and increase in respiratory system compliance seen. In the CPPV group, Pa(O2) stayed around 60 mm Hg and Pa(CO2) gradually increased. PFC treatment with conventional mechanical ventilation in acute respiratory failure proved to be a successful supportive technique to improve gas exchange at low inflation pressures.