High altitude illness (HAI) affects 42% of individuals climbing above 3000 m. The pathophysiology of HAI, including water retention remains unclear. Although decreased nitric oxide (NO) production is implicated in the pathophysiology, a recent study reported increased NO in breathes of high altitude inhabitants, apparently produced to combat the high altitude hypoxia. NO binds heme generally and impairs cytochrome P450 steroidogenic enzymes. A consequence of increased NO production may be decreased steroidogenesis. An acute cortisol deficiency may thus be the reason for water retention and oedema, and explains why dexamethasone is effective in treating some aspects of HAI.