Caudwell Xtreme Everest (CXE) is a large healthy volunteer field study investigating human adaptation to environmental hypoxia. More than 200 individuals were studied at sea-level and in four laboratories on the trek to Everest Base Camp (5,300 m). Fifteen physicians climbed high on Everest and continued the studies as they ascended; eight of these individuals reached the summit of Everest and succeeded in sampling arterial blood at 8,400 m on their descent. Core measurements included cardiopulmonary exercise testing, neuropsychological assessment, near infra-red spectroscopy of brain and exercising muscle, blood markers and daily recording of simple physiological variables. The goal of CXE is to further our understanding of human adaptation to cellular hypoxia, a fundamental mechanism of injury in critical illness, with the aim of improving the care of critically ill patients.