The cardiovascular and ventilatory effects of high-frequency jet ventilation (HFJV) and conventional ventilation (CV) were evaluated in a saline lung lavage model in piglets. After saline lavage and stabilization on CV, animals were randomized to either mode of ventilation for 4 h. Arterial blood gases, cardiac output, mean pulmonary and arterial blood pressures, and pulmonary and systemic vascular resistances were compared between groups. Alveolar-arterial oxygen gradient (AaDO2) was lower in the HFJV than in the CV group after 3 h of ventilation (p less than 0.04). The peak inspiratory pressure necessary to maintain PaCO2 within the normal range was approximately half as much in the HFJV group as in the CV group (p less than 0.005) throughout the entire study period. Mean airway pressure, cardiac output, mean pulmonary and arterial blood pressures as well as pulmonary and systemic vascular resistances were not statistically different between groups. These results suggest that in this model, HFJV produces better oxygenation with lower peak airway pressures compared to CV without producing hemodynamic compromise.