The effect of carbonic anhydrase inhibition with acetazolamide (Acz) on CO2 output (VCO2) and ventilation (VE) kinetics was examined during moderate- and heavy-intensity exercise. Seven men [24 +/- 1 (SE) yr] performed cycling exercise during control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject performed step transitions (6 min) in work rate from 0 to 100 W [below ventilatory threshold (<VET)] and to an O2 uptake corresponding to approximately 50% of the difference between the work rate at VET and peak O2 uptake [above ventilatory threshold (>VET)]. VE and gas exchange were measured breath by breath. The time constant (tau) was determined for exercise <VET by using a single-exponential model (fit between 20 s and end-exercise); the mean response time (MRT) was determined for exercise >VET by using a three-component model (fit from the start of exercise). VCO2 kinetics were slower in Acz (<VET, tau = 45 +/- 6 s; >VET, MRT = 75 +/- 10 s) than Con (<VET, tau = 34 +/- 6 s; >VET, MRT = 54 +/- 7 s). During <VET exercise, VE kinetics were slower in Acz (tau = 48 +/- 6 s) than Con (tau = 34 +/- 6 s), but >VET kinetics were faster in Acz (MRT = 85 +/- 17 s) than Con (MRT = 106 +/- 16 s). Carbonic anhydrase inhibition slowed VCO2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise. The slowed VE kinetics in Acz during exercise <VET is consistent with a mechanism coupling VE kinetics with the flow of CO2 to the lungs.