We have investigated the association of two single nucleotide polymorphisms (SNPs) at positions -384 and 114 in the human interleukin-2 (hIL-2) with multiple sclerosis (MS). For two of the -384 genotypes (G/T, T/T), we observed an association with the susceptibility to secondary progressive (SP) course of MS (P=0.005 and P=0.013, respectively). Expression level differences of the IL-2 alleles (between one- and three-fold) were not attributable to the -384 promoter polymorphism. These data indicate for the first time the relevance of the il-2 gene locus in human MS and its possible involvement in other autoimmune diseases.