The study was designed to evaluate how a bout of endurance training (ET) influences the endocrine response after head-down bed rest (HDBR). Eleven healthy males completed the study, which consisted of a 6-wk ET followed by 5 days of -6 degrees head-down HDBR. Treadmill exercise at 80% of pretraining maximal aerobic capacity (VO(2max)) was performed before and after ET as well as after HDBR. ET increased VO(2max) by 13%. The response of norepinephrine was attenuated after ET and exaggerated after HDBR (P < 0.001). The differences in epinephrine responses were not statistically significant. The responses of cortisol and plasma renin activity (PRA) were unchanged after ET and were enhanced after HDBR (P < 0.001). The response of growth hormone after HDBR was reduced (P < 0.05). Only the change in cortisol response was associated with the increment of VO(2max) after ET (r = 0.68, P < 0.01). Endurance training failed to completely prevent changes in endocrine responses seen after HDBR. Improvement of physical fitness was associated with an enhancement of the cortisol response to exercise following the period of bed rest.