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OBJECTIVE:Hyperventilation is the first response to hypoxia in high altitude (HA). Our study on rats was designed to establish an integrated hypothesis to include hyperventilation, increased activity of hypothalamicpituitary-adrenocortical axis (HPA) in response to initial exposure to hypoxia and failure of adaptation to stress in olfactory bulbectomised rats. .METHODS:Albino rats whose olfactory lobes were removed were subjected to hypoxia and hypothermic conditions. Blood and urine samples were collected at various stages to measure biochemical parameters. Rats whose olfactory systems were intact were used as controls.RESULTS:The results suggested that the olfactory system regulated pituitary function and that in rats whose olfactory lobes were removed failed to adapt to the stress created by hypoxia and hypothermia.CONCLUSIONS:Acute Mountain Sickness (AMS) is a type of stress. Normal rats when subjected to stress such as AMSare able to adapt. This adaptation is lost when the olfactory bulbs are removed. It is postulated that serotonin receptors in the hypothalamus, through the splanchnic pathway regulate stress. This mechanism is independent of ACTH – Cortisol feed back system. Perhaps irregular and rapid respiratory rhythm simulates physiological Olfactory Bulbectomy during rapid climbing and AMS manifests as a failure of stress adaptation.