The effect of high-frequency oscillatory ventilation (HFOV) settings on the distribution of lung volume (V L ) with changes in mean airway pressure (Paw), frequency (f R ) and tidal volume (V T ) remains controversial. We used computer tomographic (CT) imaging to quantify the distribution of V L during HFOV compared to static continuous positive airway pressure (CPAP). In anesthetized, supine canines, CT imaging of the entire lung was performed during CPAP and HFOV at Paw of 5, 12.5 and 20cmH 2 O, f R =5, 10, 15Hz. We found small, statistically significant decreases compared with CPAP in total and regional V L during HFOV that were greatest at lower f R and Paw. Apex and base sub-volumes underwent changes comparable to the lung overall. Increases in f R were accompanied by increases in PaO2. These finding provide additional insight into the impact of HFOV settings on the distribution of V L and suggest that there is low risk of occult regional over-distention during HFOV in normal lungs.