Inspiratory hypoxia can cause neurovascular headache which is the primary symptom responsible for acute mountain sickness (AMS). We examined if the more marked arterial hypoxaemia typical of AMS would promote an increase in vascular nitrite (NO₂^–) bioavailability to cause cerebral over-perfusion and mechanical disruption of the blood-brain barrier (BBB) since vasogenic oedema has previously been documented in hypoxia (Bailey et al. 2007). Eighteen males aged 26 (mean) ± 6 (SD) years were examined in normoxia (21% O₂) and after 6h exposure to normobaric hypoxia (12% O₂). Blood flow velocity in the middle cerebral artery (MCAv) was recorded via trans-cranial Doppler ultrasound and arterial haemoglobin oxygen saturation (SaO₂) measured via pulse-oximetry. Clinical AMS was diagnosed as described previously (Bailey et al. 2007). Venous samples were obtained from an antecubital vein and assayed for plasma NO₂^– (ozone chemiluminescence) and serum S100β (radio-immunoassay). Nine subjects developed clinical AMS (AMS+) compared to the remaining 9 who were healthy (AMS-). Hypoxia decreased (SaO₂) more markedly in AMS+ compared to AMS- (-18 ± 5 vs. -13 ± 5%, P < 0.05). However, while neither AMS nor hypoxia influenced NO₂^– or S100β (Table 1) there was a tendency towards an increase in NO₂^– in AMS+ and decrease in AMS-. MCAv decreased in hypoxia but was not different between groups. These findings suggest that increased NO₂^–bioavailability may be implicated in the pathphysiology of AMS via mechanisms independent of cerebral over-perfusion and BBB disruption.