There is considerable variation among individuals in the extent of, and the time required for, ventilatory acclimatization to altitude. Factors related to this variation are unclear. The present study tested whether interindividual variation in preascent ventilation or magnitude of hypoxic ventilatory response related to ventilatory acclimatization to altitude. Measurements in 37 healthy resting male subjects at sea level indicated a wide range (34-48 Torr) of end-tidal PCO2 values. When these subjects were taken to Pikes Peak, CO (4,300 m, barometric pressure 462 mmHg), the end-tidal PCO2 values measured on arrival and repeatedly over 19 days were correlated with the sea-level end-tidal PCO2. At 4,300 m, subjects with high end-tidal PCO2 had low values of arterial oxygen saturation (SaO2). Also, sea-level end-tidal PCO2 related to SaO2 after 19 days at 4,300 m. Twenty-six of the subjects had measurements of isocapnic hypoxic ventilatory response (HVR) at sea level. The end-tidal PCO2 values on arrival and after 19 days residence at 4,300 m were inversely related to the sea-level HVR values. Thus both the PCO2 and the HVR as measured at sea level related to the extent of subsequent ventilatory acclimatization (decrease in end-tidal PCO2) and the level of oxygenation at altitude. The finding in our cohort of subjects that sea-level end-tidal PCO2 was inversely related to HVR raised the possibility that among individuals the magnitude of the hypoxic drive to breathe influenced the amount of ventilation at all altitudes, including sea level.