To evaluate the effectiveness of high-frequency jet ventilation (HFJV) in the treatment of meconium aspiration, 28 puppies were assigned randomly to one of three ventilator techniques. After aspiration of 4 ml/kg of 20% meconium and baseline measurements on conventional ventilation (CV), the animals were ventilated for 6 h with either CV, HFJV, or HFJV combined with slow conventional ventilation (combined HFJV). Arterial and mixed venous blood gases, systemic and pulmonary arterial pressures, pulmonary capillary wedge pressure, and cardiac output were measured. Combined HFJV proved superior to the other two techniques, resulting in significantly better oxygenation and ventilation at a lower mean airway pressure (Paw). Oxygenation with standard HFJV was comparable to CV, producing Paw and Pco2values intermediate between those of CV and combined HFJV. There were no significant intergroup differences in cardiac output or the incidence of pneumothorax. Improved gas exchange was attributed to alveolar recruitment and prevention of atelectasis. Alteration of the distribution and/or clearance of meconium may also be important.