The neuroendocrine and immune systems play major roles in the adaptation and, hence, survival of the organism. 1, 2 Any “stressor” or threat to the stability or “homeostasis” of the internal milieu is counteracted by adaptive forces of the organism, collectively called “the adaptive response.” The central nervous system (CNS) effector of this response is the “stress system” with its main components, the corticotropin-releasing hormone (CRH)/arginine-vasopressin (AVP) and locus ceruleus–noradrenaline (LC-NA)/autonomic (sympathetic) neurons of the hypothalamus and brain stem. These, respectively, regulate the peripheral activities of the hypothalamic–pituitary–adrenal (HPA) axis and the systemic/adrenomedullary sympathetic nervous systems (SNS). Activation of the HPA axis and LC-NA/autonomic system result in systemic elevations of glucocorticoids and catecholamines (CAs), respectively, which act in concert to maintain homeostasis. It is primarily through the stress system that stress influences the innate and specific immune response. Since Selye’s time in the late 1930s, the adrenal glands have been known to shrink the thymus and lymph nodes. 2 Subsequently, the glucocorticoids were found to inhibit lymphocyte proliferation, migration, and cytotoxicity and to suppress the secretion of certain cytokines, such as interleukin-2 (IL-2) and interferon-γ (IFN-γ). These observations and the broad use of glucocorticoids as potent antiinflammatory/immunosuppressant agents over the last 50 years led to the initial conclusion that stress was, in general, immunosuppressive. Recently, however, there has been convincing evidence that corticotropin-releasing hormone (CRH), glucocorticoids, and CAs—as well as other products of the stress system—influence the immune response both at their baseline levels and/or at elevated levels observed during stress. aAddress for correspondence: George P. Chrousos, MD, NICHD, NIH, Bldg. 10/9D42, Bethesda, MD 20892-1583. Voice: 301-496-5800; fax 301-402-0884. Chrousog@ mail. nih. gov