High levels of interleukin 6 (IL-6) have been found in the brain tissue or cerebrospinal fluid (CSF) in several CNS disorders including Alzheimer’s disease, AIDS dementia complex, multiple sclerois, stroke, Parkinson’s disease, traumatic brain injuries, brain tumors and CNS infections. In these diseases, IL-6 is also found in blood showing that CNS conditions can elicit a peripheral immune response. A direct secretion of IL-6 from brain to blood has been shown to be a major mechanism by which the brain activates peripheral metabolic, endocrine and immune responses. However, this communication is not straightforward and other regulatory mechanisms are likely to be there. Several lines of evidence obtained in the laboratory have shown that the brain significantly modulates IL-6 production in the periphery. Evidence will be given that: (i) central inflammatory stimuli efficiently induce peripheral IL-6; (ii) central opioids are effective modulators of peripheral IL-6, and (iii) the sympathetic nervous system represents an inhibitory pathway to peripheral IL-6.