Ten adult cats received alternately high-frequency jet ventilation and conventional mechanical ventilation after aspirating 2 ml/kg 25% human meconium in saline. Equivalent mean airway pressures were maintained during the hourly ventilator changes. Aortic pressures, pulmonary artery pressures, and central venous pressures were continuously monitored. Cardiac outputs were measured, and pulmonary and systemic vascular resistances, intrapulmonary shunts, and alveolar arterial oxygen gradients were determined at regular intervals. During the first hour after aspiration, AaDO2 and Qs/Qt were lower during HFJV (P<0.05); PVR and Pa were always higher during HFJV (P<0.05). Overall, PVR, Pa, AaDO2 and Qs/Qt rose during HFJV; these changes occurred at equivalent Paw within 15 minutes of each ventilator change (P<0.05). In this meconium aspiration model, conventional mechanical ventilation was the superior form of ventilatory therapy.