Surgical stress is associated with activation of both the HPA axis and the sympathetic nervous system. Emergence from anesthesia appears to be a far more potent stimulus for both of these axes than the surgery itself. Intraoperative HPA activation can be moderate in degree and the mild cortisol elevation observed is compatible with an uneventful perioperative course. This observation was confirmed in adrenalectomized nonhuman primates where a physiologic replacement dose of cortisol was both necessary and sufficient to tolerate surgical stress. Taken together these human and nonhuman primate data suggest that the role of glucocorticoids during surgery is primarily permissive. Catecholamines appear to act in synergy with glucocorticoids during surgical stress.