Much evidence has suggested the existence of bidriectional communication between the brain and the immune system. The brain is known to modulate peripheral immunity by the autonomic nervous innervation as well as the neuroendocrine communication. This review focuses particularly on the involvement of the hypothalamo-sympathetic nervous system in the stress-induced immunosuppression. On the other hand, the immune system may signal the brain by means of signal molecules such as cytokines derived from immunological cells. Proinflammatory cytokines (interleukin-1 (IL-1), IL-6 and interferonα) act directly or indirectly on the brain cells to elicit a wide variety of autonomic, neuroendocrine and behavioral responses such as fever, anorexia, sleep, ACTH release, pain modulation and immunosuppression. These acute phase responses are also demonstrated to modulate the immune system. Thus, the brain and the immune system may act together to maintain the body homeostasis through the bidirectional communication in an integrated way.