Hypoxia and physical training alter the responses of glucoregulatory hormones to absolute work loads in opposite directions. These effects have tentatively been ascribed to changes in maximal O₂ consumption (V̇O₂(max)) and ensuing changes in relative work loads. However, hypoxia as well as training may more specifically influence the hormonal response. We therefore differentiated the influence of hypoxia, training, and V̇O₂(max), respectively, on the hormonal response to bicycle exercise. Responses to hypoxia in a low-pressure chamber (P(B) = 465 vs.730 Torr) were studied at given absolute and relative (85% V̇O₂(max)) work loads in seven endurance-trained athletes (T) and 7 age and weight-matched sedentary subjects (C). Concentrations in plasma of norepinephrine, growth hormone, adrenocorticotropic hormone, and cortisol were always closely related to the relative work load. However, the epinephrine response in T, but not in C, was at the same relative work load higher during hypoxia (5.84 ± 0.83 nmol/l) than during normoxia (4.26 ± 0.44, P < 0.05). These results indicate that the hormonal response in influenced by hypoxia and physical training, mainly via changes in the relative work load. However, in trained subjects both at rest and during exercise, an enhancing effect of hypoxia per se on the epinephrine response is seen, probably due to an increased adrenal medullary secretory responsiveness in long-term endurance-trained subjects.