OBJECTIVE To study changes in PaCO2 and PaO2 during intratracheal pulmonary ventilation (ITPV) and hybrid intratracheal pulmonary ventilation (h-ITPV) compared with conventional mechanical ventilation (CMV) in a rabbit model of respiratory failure, and to define the technique of h-ITPV that combines conventional mechanical ventilation and ITPV. METHODS Prospective, interventional study. METHODS Twelve adult New Zealand White rabbits. METHODS Surfactant deficiency was induced by saline lavage, and rabbits were randomized to either ITPV or h-ITPV. The study consisted of four phases: phase 0, CMV after saline lavage, ventilator rate 30 breaths/min; phase I, ITPV or h-ITPV initiated at the same pressure and rate as in phase 0; phase II, ITPV or 1.0 L/min h-ITPV bias flow, with peak inspiratory pressure (PIP) decreased and ventilator rate increased to achieve the lowest tidal volume while maintaining adequate gas exchange; and phase III, animals returned to CMV. RESULTS In phase I, no difference in PaCO2 was observed between ITPV, h-ITPV, or CMV. There was a decrease in PaO2 when switching from CMV to ITPV but not to h-ITPV. In phase II, it was possible to decrease PIP (average of 37% for ITPV and 36% for h-ITPV) and tidal volume (average of 64% for ITPV and 53% for h-ITPV) without compromising gas exchange (p < .05). Oxygenation tended to improve from phase 0 to the end of phase II. In phase III, PaCO2 increased (average of 71% for ITPV and 79% for h-ITPV) and pH decreased (p < .05). Normocapnia was achieved using significantly higher PIP and tidal volume, compared with phase 0 (p < .05). CONCLUSIONS ITPV and h-ITPV can effectively ventilate and oxygenate rabbits with surfactant-deficient lungs at tidal volumes and therefore pressures lower than required with CMV. Maximum benefit appears to occur at high ventilator rates. These findings suggest that both modes of ventilation may represent powerful new tools in the management of patients with acute respiratory failure. (Crit Care Med 2000; 28:774-781)