Acetazolamide, which reversibly inhibits carbonic anhydrase, is a useful diuretic in alkalotic and over-hydrated patients. In two earlier investigations we have consistently found increases in the arterial and venous oxygen saturation and tension when patients were treated with acetazolamide 15 mg·kg^-1. A plausible explanation of this phenomenon is that acetazolamide diminishes oxygen consumption. In the present study we measured oxygen uptake in 10 critically ill patients. We found a minor and statistically insignificant decrease in oxygen consumption. Nevertheless SvO₂ increased from 0.77 to 0.83 and PvO₂ from 5.9 kPa to 6.8 kPa. It is still not possible from this investigation to determine the origin of the improvement in blood oxygenation. The inhibition of carbonic anhydrase caused a CO₂ retention of 5.8% of the total CO₂ production. An increase in body stores of CO₂ of this magnitude is without clinical significance.