The effect of applying a high-frequency small-volume sinusoidal oscillation at the airway was investigated in anesthetized apneic beagle dogs (mean wt 11 kg, mean VDphys 6.6 +/- 0.6 ml/kg). Oscillations generated by a piston in a cylinder were transmitter to the lungs through an uncuffed endotracheal tube (4.5 mm ID, 6.0 mm OD), which allowed a substantial leak back through the vocal cords. A bias flow of fresh gas presented inspired air to the midtracheal level. The minimum distal airway pressure (measured at the end of the endotracheal tube) was maintained between 0 and 2 cmH2O. Peak airway pressures were 4-8 cmH2O. The optimal frequency for CO2 elimination was 15 Hz. Using volumes of 1.9 ml/kg (range 1.7-2.3) at this frequency the mean PaCO2 was 33.1 +/- 0.5 Torr. In four dogs breathing 100% O2 the PaO2 was 594 +/- 9 Torr during spontaneous ventilation and 580 +/- 9 Torr after 5 h of uninterrupted oscillation. In four experiments using room air the PaO2 was 95 +/- 5 Torr during spontaneous respiration and 106 +/- 1 Torr after 5 h of oscillation. In an additional seven studies there was no difference in mean cardiac output between oscillation and conventional mechanical ventilation. This study demonstrates that high-frequency small-volume oscillations can maintain gas exchange for many hours presumably by markedly enhancing the diffusivity of gases in the lung.