Respiratory distress syndrome carries a high morbidity and mortality when treated with mechanical ventilation with positive end-expiratory pressure. Perfluorocarbon liquids are employed in liquid ventilation due to low surface tension and high gas solubility. To assess whether intratracheal administration of the perfluorocarbon, perflubron, in combination with conventional mechanical ventilation could be of therapeutic benefit in respiratory distress syndrome, the authors tested the effects of different doses of intratracheal perflubron administration on gas exchange and lung mechanics in adult animals with respiratory failure during a 6-h observation period. Respiratory failure was induced in 30 rabbits by saline lung lavage (arterial oxygen tension < 100 mmHg at 100% oxygen with the following ventilator settings: tidal volume, 12 ml.kg-1; respiratory frequency, 30 per min; inspiratory/expiratory ratio, 1:2; and positive end-expiratory pressure of 6 cm H2O). Twenty-four rabbits were treated with different perfluorocarbon doses (3, 6, 9, and 12 ml.kg-1), and the remaining six served as controls while mechanical ventilation was continued with the aforementioned settings. Additionally, in ten healthy rabbits who were used as healthy controls, the lungs were mechanically ventilated either alone or in combination with intratracheal perfluorocarbon administration (3 ml.kg-1) for 6 h. In all treatment groups, arterial oxygen pressure increased significantly (P < 0.0001) in a dose-related fashion (193 +/- 40, 320 +/- 70, 353 +/- 125, and 410 +/- 45 mmHg at 15 min), and peak airway pressures decreased significantly (range, 18-23%; P < 0.0001) from pretreatment values. These findings were in contrast to those for the control group. The improvements were time-dependent in all four tested perfluorocarbon doses. However, the improvements in pulmonary parameters could be extended to 6 h only in groups treated with 9 ml.kg-1 and 12 ml.kg-1 perflubron. At the end of the 6-h period, the data for these two groups showed significantly higher arterial oxygen pressure (230 +/- 84 and 197 +/- 130 mmHg, respectively; P < 0.05) and lower inflation pressures than the pretreatment data for these groups and the data for the control group at 6 h. There were no clinically significant changes in pulmonary parameters in healthy animals due either to mechanical ventilation alone or mechanical ventilation in combination with intratracheal perfluorocarbon administration for 6 h. The results of this study imply that there is no association between the lung mechanics and gas exchange parameters for mechanical ventilation in combination with intratracheal perfluorocarbon administration. The data suggest that this type of perfluorocarbon administration with conventional mechanical ventilation offers a simple, alternative treatment of respiratory distress syndrome. With this technique, adequate pulmonary gas exchange can be maintained at relatively low airway pressures with high perfluorocarbon doses for several hours.