A piglet model of respiratory failure was used to compare airway pressures required for adequate gas exchange by a conventional positive pressure ventilator (CMV) and a high-frequency pneumatic flow interrupter (HFFI). Twelve newborn piglets (age means = 3.8 days and weight means = 1.4 kg) were given saline lung lavages after receiving intravenous Ketamine and Pavulon. Femoral and jugular vessels were catheterized for measurements of aortic and pulmonary blood pressures and gases, cardiac output, hematocrit, glucose and for the infusion of fluids. Airway pressures were measured 5 mm above the distal tip of the endothracheal tube. Lung lavage resulted in decreased static compliance and a twofold increase in pulmonary shunting. Following lavage the animals were kept on 100% oxygen and randomly assigned to either CMV (30/min) or HFFI (600/min) ventilation and thereafter were switched every 30 minutes to the alternate mode. Inspiratory duration was 33% of the total respiratory cycle during CMV and 30-50% for HFFI. Sixteen pairs of data comparing both ventilator modes were used. Blood gases, cardiovascular variables, alveolar-arterial oxygen gradient, and pulmonary shunting were not different with either ventilator. Positive end-expiratory pressure (5.3 and 5.6 cm H2O) and mean airway pressure (12.5 and 11.9 cm H2O) were equal for CMV and HFFI, respectively. Peak inspiratory pressure was significantly lower for HFFI (23.1 +/- 3.7 SD cm H2O) than for CMV (30.4 +/- 5.5 SD cm H2O). The lower peak inflation pressure required during HFFI ventilation may reduce the potential for lung rupture.