Exercise promotes escape of ACTH and cortisol from suppression by dexamethasone (DEX) in some healthy men and women. To determine whether stimulus strength, diurnal rhythmicity, or gender influences neuroendocrine escape during DEX suppression, we studied men (n = 5) and women (n = 5) during high intensity exercise tests after taking 4 mg DEX: two tests (one at 90% and one at 100% of maximal aerobic capacity) were conducted in the morning and two were performed in the afternoon on nonconsecutive days. Plasma ACTH and cortisol showed significantly greater increases with the 100% compared to the 90% intensity exercise (ACTH: 90%, 2 +/- 0.4; 100%, 3 +/- 0.5 pmol/L; cortisol: 90%, 53 +/- 5.3; 100% 93 +/- 23.6 nmol/L). Plasma cortisol responses were significantly higher in women than in men (P < 0.01). Plasma arginine vasopressin (AVP) exhibited significant intensity-dependent increases, with higher responses in women than men (P < 0.01). In conclusion, despite high dose glucocorticoid pretreatment, intense exercise can override the glucocorticoid negative feedback of hypothalamic-pituitary-adrenal activation in most normal men and women. This ability to override cortisol negative feedback inhibition may relate to the magnitude of the AVP response, the potency/specificity of the stressor to elicit a CRH/AVP response, and/or the sensitivity of the glucocorticoid negative feedback system at the time of the stress.