-We aimed to test effects of altitude acclimatization on pulmonary gas exchange at maximal exercise. Six lowlanders were studied at sea level, in acute hypoxia (AH), and after 2 and 8 wk of acclimatization to 4,100 m (2W and 8W) and compared with Aymara high-altitude natives residing at this altitude. As expected, alveolar PO2 was reduced during AH but increased gradually during acclimatization (61 Ϯ 0.7, 69 Ϯ 0.9, and 72 Ϯ 1.4 mmHg in AH, 2W, and 8W, respectively), reaching values significantly higher than in Aymaras (67 Ϯ 0.6 mmHg). Arterial PO 2 (PaO 2 ) also decreased during exercise in AH but increased significantly with acclimatization (51 Ϯ 1.1, 58 Ϯ 1.7, and 62 Ϯ 1.6 mmHg in AH, 2W, and 8W, respectively). Pa O 2 in lowlanders reached levels that were not different from those in high-altitude natives (66 Ϯ 1.2 mmHg). Arterial O 2 saturation (SaO 2 ) decreased during maximum exercise compared with rest in AH and after 2W and 8W: 73.3 Ϯ 1.4, 76.9 Ϯ 1.7, and 79.3 Ϯ 1.6%, respectively. After 8W, Sa O 2 in lowlanders was not significantly different from that in Aymaras (82.7 Ϯ 1%). An improved pulmonary gas exchange with acclimatization was evidenced by a decreased ventilatory equivalent of O2 after 8W: 59 Ϯ 4, 58 Ϯ 4, and 52 Ϯ 4 l⅐ min ⅐ l O2 Ϫ1 , respectively. The ventilatory equivalent of O2 reached levels not different from that of Aymaras (51 Ϯ 3 l⅐ min ⅐ l O2 Ϫ1 ). However, increases in exercise alveolar PO2 and PaO 2 with acclimatization had no net effect on alveolar-arterial PO2 difference in lowlanders (10 Ϯ 1.3, 11 Ϯ 1.5, and 10 Ϯ 2.1 mmHg in AH, 2W, and 8W, respectively), which remained significantly higher than in Aymaras (1 Ϯ 1.4 mmHg). In conclusion, lowlanders substantially improve pulmonary gas exchange with acclimatization, but even acclimatization for 8 wk is insufficient to achieve levels reached by high-altitude natives. chronic hypoxia; acute normoxia; ventilation HIGH-ALTITUDE NATIVES from North America (8), Tibet (27), and South America (19, 25) have unique pulmonary gas transport abilities, maintaining low alveolar-arterial PO 2 difference (A-aPO 2 ) at maximum exercise, thus preserving arterial PO 2 (Pa O 2 ) and saturation (Sa O 2 ). This confers a clear advantage to high-altitude natives compared with the lowlanders during exercise at altitude. Although pulmonary gas exchange in high-altitude natives has been the focus of several studies, only a few reports exist on pulmonary gas exchange during exercise in lowlanders acclimatized to high altitude. The classic study by Dempsey et al. (8) investigated lowlanders acclimatized to 3,100 m for 4, 21, and 45 days and compared these with firstto third-generation high-altitude residents. Despite the limited number of subjects analyzed (4 lowlanders), a comparatively low exercise A-aPO 2 was observed in the natives, whereas the lowlanders seemed to reduce their exercise A-aPO 2 as the altitude exposure was prolonged (8). More recently, Calbet et al. (5, 6) also found reduced exercise A-aPO 2 in seven lowlanders after chronic (9 wk) compared ...