Airway pressure during high-frequency jet ventilation (HFJV) reflects safety, ventilator performance, and gas exchange. The value of airway pressure as a monitoring and control variable for predicting the effectiveness of gas exchange was examined in 2 studies using healthy dogs. In the first study, HFJV was delivered to the airway via an extra lumen in the wall of an endotracheal tube, at a frequency of 150 cycle/min and 30% inspiratory time. Airway pressures (peak, mean, trough) were measured at various locations, from 5 cm below to 30 cm above the jet port. Pressures measured above the jet were misleading, but the proper measurement distance below the jet remains uncertain. The second study used the same ventilator settings but varied the airway pressure difference between peak and end-expiratory pressures (2, 4, or 6 cm H2O), and either the mean airway pressure (6 or 10 cm H2O) or the positive end-expiratory pressure (0, 5, 10, or 15 cm H2O). The airway pressure difference correlated strongly with efficiency of gas exchange for both CO2 elimination and oxygenation. Mean and end-expiratory pressures showed little influence over moderate ranges, but use of 15 cm H2O of PEEP decreased efficiency of both CO2 elimination and oxygenation, presumably due to increased dead space because of lung overdistension. We conclude that the airway pressure difference, measured as far distal in the airway as is safe and practical, can be useful for monitoring and controlling HFJV.