, cerebral and muscle oxygenation, and total hemoglobin mass before and after a 72-day Mt. Everest expedition. High Alt Med Biol 15:331-340, 2014.-Background: We investigated the effects of chronic hypobaric hypoxic acclimatization, performed over the course of a 72-day self-supported Everest expedition, on ventilatory chemosensitivity, arterial saturation, and tissue oxygenation adaptation along with total hemoglobin mass (tHb-mass) in nine experienced climbers (age 37 -6 years, _ VO 2peak 55 -7 mL$kg). Methods: Exercise-hypoxia tolerance was tested using a constant treadmill exercise of 5.5 km$h -1 at 3.8% grade (mimicking exertion at altitude) with 3-min steps of progressive normobaric poikilocapnic hypoxia. Breath-by-breath ventilatory responses, Spo 2 , and cerebral (frontal cortex) and active muscle (vastus lateralis) oxygenation were measured throughout. Acute hypoxic ventilatory response (AHVR) was determined by linear regression slope of ventilation vs. Spo 2 . PRE and POST (< 15 days) expedition, tHb-mass was measured using carbon monoxide-rebreathing. Results: Post-expedition, exercise-hypoxia tolerance improved (11:32 -3:57 to 16:30 -2:09 min, p < 0.01). AHVR was elevated (1.25 -0.33 to 1.63 -0.38 L$min -1. % -1 Spo 2 , p < 0.05). Spo 2 decreased throughout exercise-hypoxia in both trials, but was preserved at higher values at 4800 m post-expedition. Cerebral oxygenation decreased progressively with increasing exercise-hypoxia in both trials, with a lower level of deoxyhemoglobin POST at 2400, 3500 and 4800 m. Muscle oxygenation also decreased throughout exercisehypoxia, with similar patterns PRE and POST. No relationship was observed between the slope of AHVR and cerebral or muscle oxygenation either PRE or POST. Absolute tHb-mass response exhibited great individual variation with a nonsignificant 5.4% increasing trend post-expedition (975 -154 g PRE and 1025 -124 g POST, p = 0.17). Conclusions: We conclude that adaptation to chronic hypoxia during a climbing expedition to Mt. Everest will increase hypoxic tolerance, AHVR, and cerebral but not muscle oxygenation, as measured during simulated acute hypoxia at sea level. However, tHb-mass did not increase significantly and improvement in cerebral oxygenation was not associated with the change in AHVR.