Maximal O2 uptake (VO2max) was determined on a bicycle ergometer in chronic hypoxia (CH) and during acute exposure to normoxia (AN) in 50 healthy young men who were born and had lived at 3,600 m altitude (La Paz, Bolivia). VO2max was significantly improved (approximately 8%) by AN. However, the difference in VO2max measured in CH and AN (delta VO2max) was lower than that reported in sea-level natives (SN) who exercised in chronic normoxia and acute hypoxia. It is shown that high-altitude natives (HN) and SN have a similar VO2max in normoxia, but highlanders can attain a greater VO2max when O2 availability is reduced by altitude exposure. In addition, in HN, the higher the subject's VO2max in hypoxia, the smaller his delta VO2max. These results contrast with the data obtained in 14 lowlanders acclimatized to high altitude who showed that their delta VO2max was positively related to their VO2max in hypoxia, as previously reported in SN who exercised in acute hypoxia (A. J. Young, A. Cymerman, and R. L. Burse. Eur. J. Appl. Physiol. Occup. Physiol. 54: 12-15, 1985). Furthermore, arterial O2 saturation of HN behaved differently from acclimatized lowland natives, inasmuch as it fell less during exercise both in CH and AN. HN with high aerobic capacity display a lower exercise ventilation and a reduced arterial saturation, which could explain their inability to improve VO2max with normoxia.