Abstract. Cheung, Stephen S, Niina E. Mutanen, Heikki M. Karinen, Anne S. Koponen, Heikki Kyro ̈ la ̈ inen, Heikki O. Tikkanen, and Juha E. Peltonen. Ventilatory chemosensitivity, 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 – 7mL $ kg - 1 $ min - 1 ). 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, Sp o 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. Sp o 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 Sp o 2 , p < 0.05). Sp o 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 exercise- hypoxia, 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