Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions. The mechanisms accounting for this sex-related difference are not completely understood. Acetazolamide effectively counteracts nocturnal periodic breathing, but it has been investigated almost exclusively in men. Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women. We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women, and that acetazolamide, by leftward shifting the CO2 ventilatory response, could improve nocturnal periodic breathing at altitude in a sex-independent manner.