Association studies of proinflammatory and anti-inflammatory cytokines single nucleotide polymorphisms with multiple sclerosis (MS) in population with different ethnic background have shown inconsistent results. To study the possible role of tumor necrosis factor-alpha G-308A, interleukin-6 G-174C, interleukin-10 C-592A, C-819T, G-1082A, transforming growth factor (TGF)-beta (codons 10 and 25), and interferon-gamma T+874A polymorphisms in susceptibility to MS in Iranian population, DNA samples from 98 patients and 97 healthy controls were genotyped using polymerase chain reaction-sequence-specific primers. Analysis of the genotypes revealed a significant lower frequencies of tumor necrosis factor-alpha GA and TGF beta C/C G/G genotypes and higher frequency of TGF beta T/C G/C genotype in patients (P < 0.05). Our data suggest that these polymorphisms play a role in susceptibility to MS, which is possibly mediated by dysregulated production of these cytokines.