Intercellular adhesion molecule-1 (ICAM-1), an important molecule in leucocyte activation and migration, is expressed on the CNS endothelial cells of patients with multiple sclerosis. This study was conducted to determine whether ICAM-1 gene polymorphism influences the risk of developing multiple sclerosis in an Iranian population. We studied 157 patients with definite multiple sclerosis and 156 ethnically matched controls. The patients and the controls were genotyped for ICAM-1 gene polymorphism at codons 241 (exon 4) and 469 (exon 6). G/R241 and K/E 469 allele and genotype distribution did not show any significant difference between patient and control groups. We concluded that role of the ICAM-1 gene polymorphisms in the pathogenesis of multiple sclerosis is still controversial and should be studied further.