The influence of acetazolamide (ACZ) upon the ability to perform and sustain maximal and submaximal exercise bouts under normoxic and hypoxic conditions was examined in four groups of healthy male subjects (N = 27). ACZ (500 mg) or inert placebo (Pla) was administered prior to exercise in a quasi-randomized, double-blind, crossover fashion. ACZ was shown to lower venous pH (ACZ, 7.31 +/- 0.01, vs Pla, 7.35 +/- 0.08) and bicarbonate (ACZ, 22.4 +/- 0.27 mM, vs Pla, 25.4 +/- 0.6 mM) and to elevate urine pH (ACZ, 7.36 +/- 0.06, vs Pla, 5.84 +/- 0.19) and tended to elevate VE (P = 0.07) at rest. Peak VO2 measured using a continuous incremental protocol was unaltered in normoxia, while peak VCO2 and RER were lowered by ACZ. No significant effect of ACZ upon VO2, VCO2, RER, or heart rate (HR) was observed during submaximal exercise (75% of peak VO2) although VE was increased by 14% and time to exhaustion (EXHt) was reduced by 29%. During acute hypoxia at a simulated altitude of 4,270 m (Pbar = 446 mm Hg), no significant differences were noted in VE, VO2, VCO2, RER, HR, or arterial saturation (SaO2) at rest. Prior to exercise, venous pH (ACZ, 7.39 +/- 0.04, vs Pla, 7.44 +/- 0.007) and bicarbonate were lower with ACZ (ACZ, 21.6 +/- 0.46 mM, vs Pla, 24.2 +/- 0.25 mM), while urine pH was higher (ACZ, 7.6 +/- 0.07, vs Pla, 5.9 +/- 0.25). Other than a higher PCO2 and lower venous lactate with ACZ, no significant differences were identified at peak VO2.(ABSTRACT TRUNCATED AT 250 WORDS)