Communication between the central components of the stress response and the immune system plays an important role in susceptibility to inflammatory disease. This communication occurs through hormonal and neuronal mechanisms. Hormonal mechanisms involve activation of the hypothalamic-pituitary-adrenal (HPA) axis by immune system products, e.g. cytokines. The stimulated HPA axis regulates immune responses through the immunosuppressive effects of glucocorticoids. Neuronal mechanisms include direct innervation of immune organs. Cytokine activation of the HPA axis and the resultant glucocorticoid-induced suppression of immune and inflammatory responses represent an important mechanism whereby the central stress response modulates peripheral inflammation. Interruption of this communication is associated with exacerbation of inflammatory disease. Conversely, intracerebroventricular transplantation of hypothalamic tissue from inflammatory resistant rats into susceptible rats reduces peripheral inflammation by more than 85%.