High altitude-induced hypoxemia in 26 young adults was used to compare hypoxia parameters such as blood lactate, hypoxia-induced electrocardiogram signs, and the recently proposed plasma hypoxanthine concentration. At a Pao2of 30 mm Hg, no elevation in hypoxanthine and small increase in lactate was observed. Minimal leg exercise was added to further increase hypoxia during hypoxemia. A significant increase in lactate and considerable ST-T depression in electrocardiogram indicated hypoxia, but no change in plasma hypoxanthine was found. Work-dependent hyperventilation as a main cause of lactate elevation was excluded. Blockade of hypoxanthine breakdown by allopurinolin vivoincreased plasma hypoxanthine levels, but hypoxemia with or without leg exercise failed to consistently increase this level further. Elevations of blood lactate above the normal range were found at a Pao2of 30 mm Hg and below.SpeculationThe increased plasma hypoxanthine concentration in newborns after delivery may result from other factors, additional to hypoxia, because in mild hypoxemic hypoxia in healthy adults hypoxanthine was not elevated, although blood lactate was already increased. Cellular hypoxia is indicated by beginning of lactate elevation at a threshold level of Pao2of 30 mm Hg.