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Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O₂ transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid–base status during cycle exercise at ∼30, 50 and 90% in normoxia (F= 0.2093) and acute hypoxia (F= 0.125). In a double‐blind, order‐balanced, crossover design, six healthy, trained men (normoxic = 59 ml kg⁻¹ min⁻¹) exercised at both F values after ACZ (3 doses of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated using the other drug (placebo or ACZ). We measured cardiac output , leg blood flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple inert gas elimination technique. ACZ did not significantly affect , , LBF or muscle gas exchange. As expected, ACZ led to lower arterial and venous blood [HCO₃⁻], pH and lactate …