Dysregulation in the expression of pro- and anti-inflammatory cytokines is one of the milestones in multiple sclerosis (MS) development and progression. The aim of this study was to investigate the possible influence of TNF-alpha (-308), TGF-beta (codons 10 and 25), IL-10 (-1082, -819, -592), IL-6 (-174) and IFN-gamma (+874) polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping was performed by PCR-SSP method in 55 MS patients with relapsing-remitting form of the disease and 86 healthy subjects from Bulgarian population. We observed a statistically significant increase in the CC genotype of IL-10 -819 and -592 SNPs coupled with a decreased frequency of the TGF-beta +915 CG genotype in our MS patients (Pc<0.05). No significant differences were observed between MS patients and controls with respect to the distribution of the other cytokine gene polymorphisms investigated. Although the size of the study group is small, these results indicate that polymorphic variations of two of the major anti-inflammatory cytokines, IL-10 and TGF-beta, may play a role in MS susceptibility.