Although the effects of acetazolamide (ACZ) on ventilation during acute mountain sickness are well known, there are no studies assessing its effect on ventilatory response in chronic hypoxia. We studied this effect in patients with chronic mountain sickness (CMS). Subjects with CMS, living permanently at 4300m, were assigned in a randomized, double-blind study to 250mg/day (n=9) or to 500mg/day (n=9) of ACZ. Resting end-tidal PETO2 and end-tidal PETCO2 were measured before and after 3 weeks of acetazolamide. Ventilatory responses were evaluated by the determination of sensitivity to hypoxia and to CO 2 . After treatment ventilatory response to hypoxia increased, resting PETCO2 decreased, and ACZ caused a leftward shift in the position, but not a change in the slope of the ventilation (V˙E) versus PETCO2 relationship. There were no differences between the two doses used. ACZ administration provides a beneficial effect on respiratory function of high altitude natives with CMS and thus it can be an effective therapy for the disease.