The ventilatory responses to CO2 of high-altitude (HA) natives and patients with chronic mountain sickness (CMS) were studied and compared with sea-level (SL) natives living at SL. A multifrequency binary sequence (MFBS) in end-tidal Pco2 was employed to separate the fast (peripheral) and slow (central) components of the chemoreflex response. MFBS was imposed against a background of both euoxia (end-tidal Po2 of 100 Torr) and hypoxia (52.5 Torr). Both total and central chemoreflex sensitivity to CO2 in euoxia were higher in HA and CMS subjects compared with SL subjects. Peripheral chemoreflex sensitivity to CO2 in euoxia was higher in HA subjects than in SL subjects. Hypoxia induced a greater increase in total chemoreflex sensitivity to CO2 in SL subjects than in HA and CMS subjects, but peripheral chemoreflex sensitivity to CO2 in hypoxia was no greater in SL subjects than in HA and CMS subjects. Values for the slow (central) time constant were significantly greater for HA and CMS subjects than for SL subjects.