Background and Aims: Hypoxic vasodilatation is a conserved physiological response that couples blood flow and oxygen delivery to tissue metabolic demand. Regulatory roles for the nitrite anion (NO2-) and/or S-nitrosylhaemoglobin (HbSNO) have been widely contested given their ability to conserve and transduce nitric oxide (NO) bioactivity (Haldar et al., 2013). To provide further insight, we determined to what extent hypoxia and exercise influence local exchange measured across the cerebral and femoral circulation. Methods: Ten participants completed a normoxic and hypoxic trial (10% FIO2) with measurements performed at rest and following 30 min of cycling at a fixed power output equivalent to 35% of the maximum achieved in normoxia. Blood samples were obtained from the brachial artery (BA) and internal jugular (JV) and femoral (FV) veins. Plasma and red blood cells (RBC) were assayed for NO2- and HbSNO via ozone-based chemiluminescence (Bailey et al., 2010). Cerebral blood flow (CBF) was determined from transcranial doppler ultrasound and femoral venous blood flow (FBF) by constant infusion thermodilution. Net exchange was calculated as plasma or RBC flow × (JV or FV – RA). Data were analysed with a three factor repeated measures ANOVA and Bonferroni-corrected paired samples t-tests. Results: Both CBF and FBF were elevated during hypoxia with only the latter shown to respond to exercise (Table). Hypoxia reversed NO2- uptake resulting in net output with the greatest increase observed across the femoral circulation during exercise. Exercise elevated HbSNO output with the greatest increases confined to the femoral circulation. Both hypoxia and exercise-induced increases in FBF were associated with increased HbSNO (r = 0.68-0.72, P < 0.05) but not NO2- (P > 0.05) output. Conclusions: The present findings provide clear evidence for local NO metabolite formation and protected transport across the circulation proportional to the increase in tissue perfusion. The net output as opposed to loss of NO2-, the latter traditionally taken to reflect consumption and corresponding liberation of NO, favours HbSNO as the more likely species responsible for transferring bioactivity.