Respiration in man exposed to 5400 m was studied during sleep over a period of 6-8 h at night. Subjects were adult males, and belonged to distinct groups: one was Sherpa high altitude residents of the Himalayas and the other consisted of causasian sojourners from near sea level. All the volunteers had spent at least 32 days at or above 5400 m before the study. The subjects were instrumented for the measurements of breath-by-breath ventilation, SaO2%, eye-movement and heart rate. Nasal prongs were secured for the administration of mixtures of O2, N2 or CO2. Also, ventilatory sensitivity to hypoxia was studied in the awake state by the transient N2 and O2 tests. The lowlanders who showed high respiratory sensitivity to hypoxia also manifested periodic breathing with apnea during sleep. A raised PIO2 and SaO2% decreased ventilation, raised PACO2, attenuated respiratory oscillations and eliminated apnea in the sojourners. CO2 inhalation in air also eliminated apnea but not the periodicity, indicating that respiratory alkalosis caused apnea but periodic breathing was independent of central stimulation by CO2-H+. None of the Sherpa highlanders with low ventilatory sensitivity to hypoxia showed any sustained periodic breathing with apnea. The large breathing oscillations and periodic apnea correlated well with the ventilatory sensitivity to hypoxia (r = 0.85), supporting the hypothesis that a high gain of the peripheral chemoreflex is conductive to periodic breathing. Sherpas by attenuating chemoreflexes have reduced instability as well as cost of breathing at high altitude.