Acute mountain sickness (AMS) is a neurological syndrome triggered by the hypoxia of high-altitude that is characterised by headache and associated vegetative symptoms. It has traditionally been considered a self-limiting form of high-altitude cerebral oedema (HACE) with both syndromes sharing a common pathophysiology linked by vasogenic oedematous brain swelling that ultimately leads to intracranial hypertension (Hackett and Roach, 2001). However, recent studies have consistently failed to identify “gross” blood-brain barrier (BBB) disruption as a distinguishing event (Bailey et al., 2006, 2009a; Kallenberg et al., 2008). In contrast, severe vasogenic oedema and micro-haemorrhages are characteristic features of HACE, a life-threatening condition defined by severe truncal ataxia and clouded consciousness. To confirm these subtle structural differences across the spectrum of illness, we hypothesised that unlike subjects with severe AMS, the brains of HACE survivors would be characterised by an accumulation of insoluble iron (III) oxide-hydroxide in the form of haemosiderin deposits that we would take to reflect cerebral capillary “stress-failure” subsequent to BBB disruption. A highly-sensitive Susceptibility Weighted Imaging-MRI technique was performed 1.5-31 months following diagnosis in 3 patients who had been rescued having survived HACE (aged 26-66 years) and in 3 control subjects diagnosed with severe AMS (aged 26-47 years) following comparable altitude exposure. Multiple haemosiderin deposits indicative of micro-haemorrhages were found predominantly within the corpus callosum (corpus, splenum and genu) of HACE patients whereas no deposits were present in the AMS subjects. Additional diffusion-weighted (ADC mapping) combined with FLAIR imaging confirmed the persistence of vasogenic oedema in one subject diagnosed with HACE 6 weeks previously. These findings are the first to identify haemosiderin deposits within the corpus callosum as a novel diagnostic biomarker that distinguishes HACE from AMS. Since AMS has been associated with impaired cerebral autoregulation (Bailey et al., 2009b), the more severe arterial hypoxaemia characteristic of HACE may, in the setting of hypoxic cerebral vasodilatation, force a pressure-passive increase in cerebral blood flow and capillary hydrostatic pressure that ultimately leads to mechanical failure of the BBB. The long-term neurological impact of capillary stress-failure within the corpus callosum of HACE survivors remains to be examined.