Little is known with regard to how acute and chronic high altitude exposure effects immune function. Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine function. Alterations in these systems can have an immediate as well as a longer lasting impact on immune function. Studies from the summit of Pikes Peak (4300 m) have indicated a strong alpha- & beta-adrenergic component in the regulation of immune function at altitude that can persist weeks after initial exposure. Specifically, interleukin (IL)-6 is elevated with acute altitude exposure primarily mediated via beta-adrenergic stimulation and remains elevated for several weeks as a result of alpha-adrenergic activation. When the added stress of physical exercise is combined with that of hypoxia, a more pronounced impact on immune function is observed compared to that of either exercise or hypoxia alone. A popular training paradigm currently employed by endurance athletes to enhance performance involves living at high altitude while training at low altitude. The concept entails incorporating the physiologic and metabolic adaptations associated with chronic high altitude exposure (increase in RBC, mitochondrial oxidative capacity, capillary density, etc) while training at a lower altitude allowing for the maintenance of a high absolute training intensity. Others have demonstrated that a short-term application (18 days) of the live high-train low paradigm results in suppression of the mucosal immune system as indicated by a cumulative decline in salivary IgA levels. Taken together, the majority of evidence suggests a potential additive effect of combined hypoxia and exercise in transiently suppressing immune function, at least in the short-term. Implications for the athletes and training are addressed.