Proinflammatory cytokines with immunosuppressive properties play an important role in the pathogenesis of multiple sclerosis (MS). Interleukin 18 (IL-18) is one of the most important innate cytokines produced from macrophages in the early stages of the inflammatory immune response. The purpose of this study was to determine whether there was any relationship between IL18 gene polymorphisms and MS. IL18 genotyping were performed in 101 MS patients and 164 control subjects by using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of MS patients with the CC genotype of the IL18 gene at position -137 was significantly higher than with the GG genotype [p = 0.01, odds ratio (OR) 3.17]. In haplotype analysis of two SNPs in the IL18 gene, frequency of the CC haplotype was significantly higher in MS patients (p = 0.002, OR 3.0). However, the genotype distribution of the IL18 -607 C/A polymorphism in the MS patient group was not significantly different from that of the control group. These data suggest that IL18 gene polymorphisms at position -137 might be a genetic risk factor for MS in the Turkish population.