The purpose of this study was to demonstrate that ventilation of rabbit lungs (whose mechanics are similar to those of human infants) at rapid rates will lead to large alterations in tracheal airway pressures, tidal volume, and functional residual capacity (FRC) with only minor changes in arterial blood gases. Thirteen rabbits were ventilated at rates of 30, 60, 90, and 120 breaths per minutes (BPM) with pressures of 17/2 cm H2O. Tracheal peak inspiratory pressure (PIP) was always lower than ventilator PIP and decreased to 11 +/- 1 cm H2O at 120 BPM. Positive end-expiratory pressure (PEEP) in the trachea was always greater than 2 cm H2O and increased with rate (3.5 cm H2O at 120 BPM). Tidal volume decreased as rates were increased such that rates above 60 BPM resulted in insignificant changes in minute ventilation and arterial blood gases. However, the FRC increased from 16 (30 BPM) to 25 ml/kg (120 BPM), a 56% increase, suggesting large increases in end-expiratory alveolar pressure. We conclude that rapid-rate ventilation (greater than 60 BPM) of healthy rabbits results in significant increases in both tracheal PEEP and FRC without significantly affecting arterial blood gases. The increased tracheal PEEP and FRC are manifestations of inadvertent PEEP. The increased FRC without concomitant increase in PaO2 implicates alveolar overdistention. We speculate that rapid-rate ventilation of human infants having lung mechanics similar to rabbits, will also result in inadvertent PEEP and alveolar overdistention.