We wished to determine in a laboratory animal model how much residual lung was needed to sustain total gas exchange. In a series of young, healthy lambs weighing approximately 10 kg that were sedated and paralyzed, we progressively excluded from gas exchange all the left lung (a total of 43%), plus the right lower and cardiac lobes (81%), plus the right middle lobe (87.5%). In some studies, the respective lobes were surgically removed; in others, the bronchi and the pulmonary arteries to the respective lobes were ligated. We provided pulmonary ventilation using the pressure control mode (Servo 900 C) at a tidal volume of 20 mL/kg multiplied by the fraction of the remaining lungs, a respiratory rate up to 120/min, a peak inspiratory pressure of 12–15 cm H2O, and a positive end-expiratory pressure of 3 cm H2O. Those lambs with at least both the right upper lobe (RUL) and right middle lobe remaining (19% of total lungs) were weaned to room air on mechanical ventilation within 48 h. Ventilating RUL (12.5% of remaining lung) with the same ventilator required a substantially higher tidal volume and peak inspiratory pressure to result in adequate alveolar ventilation but led to respiratory failure and death within 8 h. We then applied a newly developed system of intratracheal pulmonary ventilation to ventilate the RUL (12.5% of remaining lung) alone. A continuous flow of humidified mixture of air and oxygen was directly passed into the trachea at the level of the carina through a diffuser at a tidal volume of 2.5 mL/kg. A single valve controlled expiration and respiratory rate. Lambs with only RUL remaining were weaned to room air within 2 h, at a respiratory rate of 60–120/min and peak inspiratory pressure of 14–9 cm H2O, inspiration to expiration ratio of 1:1, and positive end-expiratory pressure of 3 cm H2O. Initial mean pulmonary artery pressure progressively decreased from 40 ± 5 to 25 ± 7 mm Hg within 6 h after surgery.