Neuroendocrine-immune interactions are profoundly regulated by corticotropin-releasing hormone (CRH) indirectly, through activation of a global stress response, and directly, through pro-inflammatory actions on peripheral immune functions. The indirect effects of stress on immune/inflammatory responses occur via the stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenomedullary system. We have demonstrated that glucocorticoids and catecholamines favor T helper 2 (TH2) over T helper 1 (TH1) immune cells and mediators, by controlling the production of specific key regulatory cytokines. This could explain the influences of chronic stress on the development, course, and pathology of certain allergic, autoimmune/inflammatory, infectious, and neoplastic diseases. We have also shown that 'immune CRH' is secreted peripherally and plays a direct immunomodulatory role as an autocrine or paracrine mediator of inflammation. Upon release from immune cells and peripheral sensory afferent and/or postganglionic sympathetic nerves, CRH acts locally to elicit pro-inflammatory responses. This would explain the triggering or exacerbation of certain allergic or vasokinetic states by acute stress.