Transient ventilatory response to 3 and 5 breaths of N 2 at rest and during exercise at sea level was determined in three high altitude natives acclimatized for 10 months and in three sea level natives. The striking differences were: 1) in the highlanders ventilation increased only when P a O 2 fell to 50–60 mm Hg, whereas in the lowlanders any decrease in P a O 2 from the resting value augmented ventilation; and 2 the increase in ventilation with P(Spao)In2 reduction was much less in the highlanders. The relative increase in ventilation during exercise from euoxic to hypoxic levels was also less in the highlanders than in the lowlanders. Transient relief of hypoxia at 4540 m by 2 breaths of O 2 during rest decreased ventilation by 10 per cent in the highlander and by 37 per cent in the lowlander. Thus ventilatory drive to transient O 2 stimulus in the highlander is low, and it remains low even after prolonged stay at sea level, suggesting irreversible insensitivity of the peripheral arterial chemoreflex mechanism to hypoxia.