The central nervous system (CNS) is considered to be an immune-privileged site. Entry of lymphocytes into the CNS is tightly controlled by endothelium, which is an important component of the blood-brain barrier (BBB). Under physiologic conditions, lymphocyte traffic into the CNS is low, whereas during inflammatory diseases of the CNS such as multiple sclerosis (MS) or in the animal model experimental autoimmune encephalomyelitis (EAE) large numbers of circulating lymphocytes readily gain access to the CNS later during disease facilitated by the loss of BBB integrity. Thus, the interaction of circulating inflammatory cells with endothelium is a critical step in the pathogenesis of EAE.