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 4300 m, were assigned in a randomized, double-blind study to 250 mg/day (n = 9) or to 500 mg/day (n = 9) of ACZ. Resting end-tidal PE TO2 and end-tidal PE TC O2 were measured before and after 3 weeks of acetazolamide. Ventilatory responses were evaluated by the determination of sensitivity to hypoxia and to CO2. After treatment ventilatory response to hypoxia increased, resting PE TC O2 decreased, and ACZ caused a leftward shift in the position, but not a change in the slope of the ventilation (over(V, ̇) E) versus PE TC O2 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. © 2008 Elsevier B.V. All rights reserved.