Background Cytokine gene polymorphisms have been extensively studied in association with different diseases. The role of cytokine gene polymorphisms in multiple sclerosis (MS), as a chronic immune-mediated neurodegenerative disease, has been previously reported. Materials and methods DNA samples were collected from 44 patients with relapsing-remitting multiple sclerosis (RRMS) and 140 unrelated healthy subjects. All participants in this study were matched for ethnicity. Cytokine gene SNPs were determined using the PCR-SSP method. Results and discussion We found no significant differences between MS patients and controls in most of the studied cytokine genes. Remarkable results were obtained for IL-2 GG —330 genotype (P = 0.06), IL-6 C —174 allele (P = 0.06), CG and GG genotypes (P < 0.001), and GG (P = 0.02) and CG (P < 0.001) haplotypes, and TNF-α A —238 allele (P < 0.001), GG (P = 0.003) and GA (P < 0.001) haplotypes. These results suggest that polymorphic variations of these pro-inflammatory cytokines play an important role in susceptibility to MS. Multiple Sclerosis 2007; 13: 253–255. http://msj.sagepub.com