Theiler’s murine encephalomyelitis virus (TMEV) causes demyelination with inflammation of the central nervous system (C NS) in mice and is used as an animal model for multiple sclerosis (MS). Interferon-g inducible protein-10 kDa (IP-10) is a C XC chemokine and a chemoattractant for C XC R3⁺ T cells. IP-10 mRNA is expressed in the C NS during TMEV infection. However, administration of anti-IP- 10 serum caused no difference in clinical signs, inflammation, demyelination, virus persistence or anti-virus antibody response in TMEV infection, while levels of virus specific and autoreactive lymphoproliferation increased. This likely reflects a difference in the pathogenesis of TMEV infection from that of two other animal models for MS, mouse hepatitis virus infection and experimental allergic encephalomyelitis (EAE), where blocking of IP-10 resulted in clinical and histological improvement with suppression of antigen specific lymphoproliferation. In this review, we compare and contrast the roles of IP-10 between the three animal models for MS, and discuss the relevance to MS patients with different clinical courses.