A single nucleotide polymorphism (SNP) at position -376 of the tumor necrosis factor alpha gene (TNFA) has been associated with susceptibility to multiple sclerosis (MS) in Spain. However, no association was found in populations from the USA and The Netherlands. Here we investigate the association between the TNFA-376A SNP and MS susceptibility in Argentinean patients with MS. The A/G genotype was found in 4.4% of patients (n=90) and in 4.8% of healthy individuals (n=84; p=0.92; odds ratio=0.93; confidence interval: 0.23-3.84). Thus, no significant differences in genotype and allele frequencies were found between healthy individuals and patients with MS in Argentina.