To determine the effects of mean airway pressure on hemodynamics during high-frequency ventilation, we ventilated five cats (wt 2.8 ± 0.6 kg) using both HFOV (frequencies 3 to 20 Hz) and HFJV (frequencies 4 to 8 Hz) at P̄aw values ranging from 2 to 12 cm H2O. Combinations of frequency and tidal volume that maintained normocapnia were employed in random order before and after reduction of static compliance of the respiratory system by lung lavage. Heart rate was comparable during both modes of high-frequency ventilation. During both HFOV and HFJV, the cardiac output decreased and PVR increased in normal and surfactant-deficient cats as P̄aw was elevated (all p < 0.01, ANOVA). For both HFOV and HFJV linear regression of P̄aw and cardiac output yielded comparable slopes and y-intercepts. Lung lavage reduced the effect of P̄aw but did not eliminate it. Changes in ventilatory frequency did not affect cardiac output or PVR. We conclude tht the interaction between high-frequency ventilation and cardiovascular function is largely determined by P̄aw and compliance and is independent of ventilator frequency and the type of ventilator used.