Elevated pulmonary arterial pressure in high-altitude residents may be a maladaptive response to chronic hypoxia. If so, well-adapted populations would be expected to have pulmonary arterial pressures that are similar to sea-level values. Five normal male 22-yr-old lifelong residents of > or = 3,600 m who were of Tibetan descent were studied in Lhasa (3,658 m) at rest and during near-maximal upright ergometer exercise. We found that resting mean pulmonary arterial pressure [15 +/- 1 (SE) mmHg] and pulmonary vascular resistance (1.8 +/- 0.2 Wood units) were within sea-level norms and were little changed while subjects breathed a hypoxic gas mixture [arterial O2 pressure (PaO2) = 36 +/- 2 Torr]. Near-maximal exercise [87 +/- 13% maximal O2 uptake (VO2max)] increased cardiac output more than threefold to values of 18.3 +/- 1.2 l/min but did not elevate pulmonary vascular resistance. Breathing 100% O2 during near-maximal exercise did not reduce pulmonary arterial pressure or vascular resistance. We concluded that this small sample of healthy Tibetans with lifelong residence > or = 3,658 m had resting pulmonary arterial pressures that were normal by sea-level standards and exhibited minimal hypoxic pulmonary vasoconstriction, both at rest and during exercise. These findings are consistent with remarkable cardiac performance and high-altitude adaptation.