Interferon- gamma (IFN- gamma) is an important immune regulator and inflammatory cytokine which is implicated in the pathogenesis of multiple sclerosis (MS). A single nucleotide polymorphism, T to A, at position +874 in the first intron has previously been shown. This polymorphism is associated with IFN- gamma production level. To study the effect of this polymorphism on susceptibility to multiple sclerosis, we screened genomic DNA samples from clinically definite MS patients and their unaffected first-degree relatives as controls, using sequence-specific primers (PCR-SSP). The results indicated that MS patients showed a lower TT (21.2% vs. 30.3%) and higher AA (21.2% vs. 12.1%) genotypes compared to controls, although there were statistically no differences in the IFN- gamma genotype distribution between these two groups. Thus, our data indicate that there is no association between IFN- gamma +874 polymorphism and MS susceptibility or severity of the disease.