To evaluate the role of genetic and environmental factors in the genesis of large lungs in high-altitude natives, we measured forced vital capacity (FVC), static lung pressure-volume characteristics and maximum expiratory flow-volume loops in 17- to 20-yr-old Peruvian natives to 3,850 m (highlanders) and 800 m (lowlanders). Forced vital capacity was 5.11 +/- 0.64 liters in highlanders, 116 +/- 11% of predicted; and 3.73 +/- 0.32 liters in lowlanders, 84 +/- 7% of predicted. Lung elastic recoil at functional residual capacity and at total lung capacity, and size-corrected pressure volume curves were similar in the two groups. Despite the larger volumes in highlanders, density-corrected maximum flow rates were similar in highlanders and lowlanders, and flow expressed in FVC'S-S-1 was less in highlanders. Upstream conductance at 50% FVC expressed in fvc's-s-1-cmH2O was 0.094 +/- 0.023 in highlanders vs. 0.147 +/- 0.050 in lowlanders. Flow rates did not change in sojourners to altitude, suggesting that the lower values of highlanders were due to anatomic factors. These findings suggest that airways, which form in fetal life, do not participate in adaptation to altitude, and that the large lungs of highlanders result from postnatal environmental hypoxic stimulation of lung growth. Our results illustrate the importance of "dysynaptic" lung growth in determining patterns of adult lung function.