Inflammatory demyelinating diseases comprise a heterogeneous group of disorders that affect the peripheral and central nervous system. Multiple sclerosis (MS) is the most common disease affecting the CNS white matter. Close similarities between MS and the animal model of the disease, experimental allergic encephalitis (EAE), have suggested that MS might be an autoimmune disease, which is triggered by an infectious agent. Our laboratory has directed its effort in identifying and designing therapies that interfere with key signaling pathways that mediate CNS inflammation in experimental allergic encephalitis. These have included naturally occurring cytokines such as TGFbeta and synthetic small molecules, lysofyline and tyrphostin, which inhibit the inflammatory response and prevent the development of EAE.