Aerobic exercise capacity is decreased at altitude because of combined decreases in arterial oxygenation and in cardiac output. Hypoxic pulmonary vasoconstriction could limit cardiac output in hypoxia. We tested the hypothesis that acetazolamide could improve exercise capacity at altitude by an increased arterial oxygenation and an inhibition of hypoxic pulmonary vasoconstriction. Resting and exercise pulmonary artery pressure (Ppa) and flow (Q) (Doppler echocardiography) and exercise capacity (cardiopulmonary exercise test) were determined at sea level, 10 days after arrival on the Bolivian altiplano, at Huayna Potosi (4700 m), and again after the intake of 250 mg acetazolamide versus a placebo thrice a day for 24 hours. Acetazolamide and placebo were administered double-blind and in a random sequence. Altitude shifted Ppa/Q plots to higher pressures and decreased maximum O₂ consumption (VO₂max). Acetazolamide had no effect on Ppa/Q plots, but increased arterial O₂ saturation at rest, from 84 ± 5 to 90 ± 3 % (p<0.05), and at exercise, from 79 ± 6 to 83 ± 4 % (p<0.05), and VO2 at the anaerobic threshold (V slope method), from 21 ± 5 to 25 ± 5 ml/min/kg (p<0.01). However, acetazolamide did not affect VO2max (from 31 ± 6 to 29 ± 7 ml/kg/min), and the maximum respiratory exchange ratio decreased from 1.2 ± 0.06 to 1.05 ± 0.03 (p<0.001). We conclude that acetazolamide does not affect maximum exercise capacity or pulmonary hemodynamics at high altitudes. Associated changes in the respiratory exchange ratio may be due to altered VCO₂ kinetics.