Serial rest and upright cycle exercise 2-dimensional echocardiographic studies were performed in 7 healthy young men during acclimatization to a simulated altitude of 29,000 feet (barometric pressure [PB] 240 torr) in a chamber for 40 days. In all subjects left ventricular (LV) end-diastolic, end-systolic and stroke volumes progressively decreased, with mean reductions of 21%, 40% and 14%, respectively, on ascent to 25,000 feet (PB 282 torr) at rest, and reductions of 23%, 43% and 14% during 60-W exercise. At PB 282 torr, mean arterial blood O2 partial pressures were 37 torr (rest) and 32 torr (exercise), with corresponding O2 saturations of 68% and 59%. All 3 indexes of LV systolic function examined--ejection fraction, ratio of peak systolic pressure to end-systolic volume and mean normalized systolic ejection rate at rest--were sustained in all subjects at high altitude despite reduced preload, pulmonary hypertension and severe hypoxemia. Increases in ejection fraction of 6% at rest and 10% during exercise developed at PB 282 torr and a higher mean normalized systolic ejection rate in association with elevated circulating catecholamines reflecting enhanced sympathetic activity. LV systolic function is not a limiting factor in compromising the exercise capacity of normal humans on ascent to high altitude, even to the peak of Mt. Everest.