Ventilatory requirements during simulated aeromedical transportation were investigated in normal dogs and animals with oleic acid-induced lung injury. Inspired oxygen fractions of 0.21 and 1.0 were used to ventilate the normal and injured dogs, respectively. Both groups were ventilated with a constant-volume piston ventilator. After a control period, animals were exposed to a simulated altitude of 8,000 ft (barometric pressure 564 mm Hg), followed by a second control period at ground level. Both groups of animals had no change in carbon dioxide production, arterial PCO2 or ventilation during exposure to reduced barometric pressure. Systemic blood pressure, heart rate, cardiac output, and lung volume were all lower in oleic acid-injured animals than controls; the alveolar-arterial oxygen difference was larger in the oleic acid group. With altitude exposure, arterial and mixed venous oxygen tensions were decreased in both groups. Adequate gas exchange can be maintained during exposure to altitude even in animals with abnormal function provided that ventilation is constant and the inspired oxygen fraction is increased to compensate for the reduced barometric pressure.