Using the radiolabeled microsphere technique, the authors studied hemodynamic variables and regional blood flow to multiple peripheral organs during conventional positive-pressure ventilation (CV) and high-frequency ventilation (HFV) at low and high mean airway pressure (Paw). Twenty supine anesthetized, paralyzed dogs were ventilated using CV (14–16 breaths/min) and HFV (rate = 10 Hz) in random order. In the first group (low Pawn = 10), Pawwas maintained at 3 cmH2O during CV and HFV. In the second group (high Paw, n = 10), Pawwas increased to 13 cmH2O during CV and HFV. Pulmonary capillary wedge pressure and right atrial pressure remained constant during low and high Pawtrials. No differences in heart rate, systemic arterial pressure, intracranial pressure, or cardiac output were noted during CV and HFV within the low and high Pawgroups. In addition, blood flow to multiple peripheral organs during CV and HFV remained constant within each Pawgroup, except for a small decrease in cerebellar blood flow during HFV at high Paw. Comparison of hemodynamic measurements during high and low Pawtrials showed a significant decrease in hepatic arterial and outer kidney cortical flow at high Paw. Total cerebral blood flow was decreased at high Paw, as were regional flows to diencephalon, midbrain, pons, medulla, and cerebellum. However, these differences were not attributable to differences in cerebral perfusion pressure or intracranial pressure, and cerebral oxygen delivery was not different between high Pawand low Pawgroups. It is concluded that under conditions of similar Pawin anesthetized dogs, HFV does not significantly alter hemodynamic patterns or regional circulation relative to CV.