Although high-frequency jet ventilation may reduce barotrauma, the optimal ventilator settings at which complications are minimized have not been determined. To develop ventilator strategies applicable to the human infant, we studied six New Zealand rabbits before and after saline lung lavage. Changes in functional residual capacity (delta FRC) and airway pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) were measured while inspiratory time (TI) and expiratory time (TE) were varied. Frequencies of 120, 240, and 480 cycles per minute and inspiratory to expiratory ratios of 1:1, 1:3, 1:5, and 1:9 resulted in TI that varied from 12 to 250 msec, and TE from 62 to 450 msec. Analysis of variance demonstrated that as TI was shortened, a significantly higher airway pressure gradient was necessary to maintain a constant tidal volume. As TE was shortened, air trapping, as determined from both inadvertent positive end-expiratory pressure and delta FRC, significantly increased. Lung lavage increased the airway pressure gradient at each TI, but decreased air trapping at each TE. At no time did entrainment contribute to the delivered tidal volume. We conclude that a relatively narrow range of TI and TE may be necessary for optimal use of high-frequency jet ventilation to reduce airway pressures and minimize the risk of air trapping.