High altitude natives are reported to have outstanding work capacity in spite of the challenge of oxygen transport and delivery in hypoxia. To evaluate the developmental effect of lifelong exposure to hypoxia on aerobic capacity, VO2peak was measured on two groups of Peruvian Quechua subjects (18-35 years), who differed in their developmental exposure to altitude. Male and female volunteers were recruited in Lima, Peru (150 m), and were divided in two groups, based on their developmental exposure to hypoxia, those: a) Born at sea-level individuals (BSL), with no developmental exposure to hypoxia (n = 34) and b) Born at high-altitude individuals (BHA) with full developmental exposure to hypoxia (n = 32), but who migrated to sea-level as adults (>16-years-old). Tests were conducted both in normoxia (BP = 750 mm Hg) and normobaric hypoxia at sea-level (BP = 750 mm Hg, FiO2 = 0.12, equivalent to 4,449 m), after a 2-month training period (in order to control for initial differences in physical fitness) at sea-level. BHA had a significantly higher VO2peak at hypoxia (40.31 +/- 1.0 ml/min/kg) as compared to BSL (35.78 +/- 0.96 ml/min/kg, P = 0.001), adjusting for sex. The decrease of VO2peak at HA relative to SL (DeltaVO2peak ) was not different between groups, controlling for baseline levels (VO2peak at sea-level) and sex (BHA = 0.35 +/- 0.04 l/min, BSL = 0.44 +/- 0.04 l/min; P = 0.12). Forced vital capacity (controlling for height) and the residuals of VO2peak (controlling for weight) had a significant association in the BHA group only (r = 0.155; P = 0.031). In sum, results indicate that developmental exposure to altitude constitutes an important factor to determine superior exercise performance.