We have evaluated the role of the HLA-DRB1*1501 allele and the IL-2 -330 T/G polymorphism and their interaction in susceptibility to multiple sclerosis on 360 patients and 426 matched healthy individuals. We used the SSP-PCR method to determine the alleles. Fisher's exact test was used to analyses. We observed a significant increase in the T allele at IL-2 -330 position in patients (OR=1.34, P<0.05), and the T/T and T/G genotypes were more frequent among patients than controls. The HLA-DRB1*1501 allele was overrepresented in patients as compared to the control group (OR=1.7, P=0.0006). The two-locus analysis of the interaction between the IL-2 promoter polymorphism and the HLA-DRB1 allele showed that the HLA-DRB1*1501/T haplotype was more frequent in patients than controls (OR=16, P<0.0001). Our findings support previous findings about the role of the HLA-DRB1*1501 allele in susceptibility to MS. This work also provides new findings about the importance of gene-gene interactions in the development of MS.