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Background Altitude illness is frequent in high altitude exposed patients. Exercise test under hypoxia could predict severe high altitude illness. Brain natriuretic peptid level seems to be higher in patients with severe high altitude illness. Purpose The aim of the study was to assess brain natriuretic peptid evolution before and after exercise test under hypoxia in order to improve severe high altitude illness screening. Methods This is a prospective single center study including all subject without contraindication to high-altitude exposure. Exercise test with normoxia and hypoxia was performed with four phases (rest under normoxia, rest under hypoxia, exercise under hypoxia, exercise under normoxia). Results We included twenty-one subjects whom five were considered at risk of severe high altitude illness. Mean brain natriuretic peptid level raised significantly after hypoxia exercise test. That was particularly marked in high-risk subjects (22.6 pg/mL to 26.4 pg/mL vs 18.4 pg/mL vs 20.2 pg/mL, P = 0.86). Conclusion Brain natriuretic peptid seems to raise more in subjects at high risk of severe high-altitude illness than other subjects. Brain natriuretic peptid level evolution could improve severe high altitude illness screening. [ABSTRACT FROM AUTHOR]