We have previously documented the importance of the sympathetic nervous system in acclimatizing to high altitude in men. The purpose of this investigation was to determine the extent to which α-adrenergic blockade affects the sympathoadrenal responses to exercise during acute high-altitude exposure in women. Twelve eumenorrheic women (24.7 ± 1.3 yr, 70.6 ± 2.6 kg) were studied at sea level and on day 2 of high-altitude exposure (4,300-m hypobaric chamber) in either their follicular or luteal phase. Subjects performed two graded-exercise tests at sea level (on separate days) on a bicycle ergometer after 3 days of taking either a placebo or an α-blocker (3 mg/day prazosin). Subjects also performed two similar exercise tests while at altitude. Effectiveness of blockade was determined by phenylephrine challenge. At sea level, plasma norepinephrine levels during exercise were 48% greater when subjects were α-blocked compared with their placebo trial. This difference was only 25% when subjects were studied at altitude. Plasma norepinephrine values were significantly elevated at altitude compared with sea level but to a greater extent for the placebo (↑ 59%) vs. blocked (↑ 35%) trial. A more dramatic effect of both altitude (↑ 104% placebo vs. 95% blocked) and blockade (↑ 50% sea level vs. 44% altitude) was observed for plasma epinephrine levels during exercise. No phase differences were observed across any condition studied. It was concluded that α-adrenergic blockade 1) resulted in a compensatory sympathoadrenal response during exercise at sea level and altitude, and 2) this effect was more pronounced for plasma epinephrine.