The effect of a sojourn of 5 days at an altitude of 14,300 feet (White Mountain, Cal.) on the alveolar-arterial oxygen gradient (A-aDo2) in the anesthetized dog was studied at three levels of oxygenation. Two dogs breathed 11% o2, air and 100% o2 at sea level, and air, 40%, and 100% o2 at altitude, with ventilation kept constant by means of a respiration pump. The alveolar samples were analyzed for o2 and CO2 pressures with the Scholander apparatus and the arterial o2 pressures were measured in an in vitro polarograph. Control studies showed that the pump itself and hyperventilation had no effect on the A-aDo2. The average values of A-aDO2, 8.6, 23.4 and 168.5 mm Hg, at sea level (the three values refer to the respective three levels of oxygenation; the last figure corresponds to a shunt of about 12% of cardiac output) agreed well with previous data. The corresponding average values of A-aDO2 at altitude were: 3.3, 17.0 and 58.0 mm Hg (corresponding to a shunt of about 4%). The A-aDO2 breathing air was lower at altitude than when breathing an equivalent oxygen tension at sea level. The most dramatic effect consisted in a threefold decrease of the A-aDO2 with 100% O2 at altitude, indicating a decrease in true veno-arterial shunt flow. Submitted on February 8, 1960