The hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) systems are implicated in the human stress response. One characterization of these systems is that they are nonspecific in their response, but differ in activation threshold and time course. Additionally, they have been found to be affected commonly by strong metabolic stressors and infusions of CRH, and a hypothesis has been developed primarily from animal research that CRH stimulates both the HPA and SAM systems. To determine whether CRH was significantly involved in tonic as well as psychological stress-induced catecholamine levels in man, we infused 24 normal male undergraduate students with either saline (n = 12) or dexamethasone (DEX; n = 12) and evaluated their subsequent plasma levels of ACTH, cortisol, epinephrine (EPI), and not epinephrine (NEPI). DEX produced a dramatic decrease in ACTH and cortisol levels, but no significant changes in EPI or NEPI occurred over a 4-h sampling interval. After the administration of math and speech stressors in a controlled laboratory setting, DEX inhibited the ACTH and cortisol release that was noted in the saline group, but stress-induced increases in EPI and NEPI were comparable in both groups. Thus, our study suggests that there is a difference in the neural pathways for tonic and stress-induced stimulation of the SAM and HPA systems.