C-C chemokine receptor 2 (CCR2) is a receptor for chemoattractant protein-1 (MCP-1) and associated with infiltrating lymphocytes in chronic active multiple sclerosis (MS) lesions. To study the role of CCR2 gene in the development of MS, we investigated the CCR2-64I polymorphism in 122 MS patients and 112 healthy controls in a Japanese population. We also analysed the influence of CCR2-64I polymorphism on the clinical course, age at disease onset, and severity. The distribution of the CCR2-64I allele was significantly different between patients and controls (p=0.0187), and the 64I/64I homozygote was significantly less common in MS than in control. Logistic analysis, adjusted for HLA-DRB1*1501-positivity, revealed negative association between the CCR2-64I and MS (p=0.0204). There were no significant associations between CCR2 polymorphism and the clinical features of MS. Our results indicate that the presence of CCR2-64I allele seems to provide protection against the development of MS.