Multiple sclerosis (MS) is a chronic autoimmune disorder that causes inflammatory demyelination and axonal damage in the central nervous system (CNS). We have investigated whether the A49G single nucleotide polymorphism (SNP) genotype of the CTLA-4 gene influenced the development of MS in Southern Australians as well as the interaction of this SNP with the DRB1*15 haplotype. There were no significant (P<0.05) associations between the A49G genotype and risk of MS, either before or after stratification for presence of the DR15 haplotype.