Background: Although the immunopathogenesis of multiple sclerosis (MS) has been intensely investigated in recent years, some associated molecules still have not been examined. For instance, no study has been conducted to investigate a possible polymorphism in the fractalkine receptor gene. Methods: In order to examine fractalkine gene receptor polymorphisms, 3 mL of serum from 92 MS patients and 91 controls were stored at -20 degrees C. DNA was extracted from the serum samples that were purified, and the gene regions in CX3CR1 (i.e., the fractalkine regions) containing the T280M and V294I fractalkine receptor haplotypes were amplified via the polymerase chain reaction (PCR) technique. The obtained fragments were then cut using restriction enzymes, and agarose gel electrophoresis was performed. Results: In a comparison of the patients and controls, we found that the median values of the Expanded Disability Status Scale (EDSS) scores among genotypes of the V294I polymorphism in the fractalkine gene receptor were statistically higher in genotype II than genotype VI. Also, relapsing/remitting MS (RRMS) was statistically higher in genotype VI than in genotype II, whereas the frequency of secondary progressive MS (SPMS) was statistically higher in genotype VV than in the genotype VI for the same polymorphism. Conclusions: Although many polymorphism studies have focused on patients with MS, there is no polymorphism study about the fractalkine receptor which is a chemokine and plays an important role in neuroinflammation and neurodegeneration. Our results provide information about disease progression and may also be beneficial in developing new strategies for the treatment of the disease.