We studied the putative association of a C-->T polymorphism in exon-5 of IL-1beta and an 85 bp tandem repeat in intron-4 of IL-1 receptor antagonist (IL-1ra) genes with susceptibility to or outcome of MS. DNA from 122 cases from a population-based cohort in Olmsted County, MN who were previously categorized for disease severity and temporal course and 244 ethnically-matched controls were analyzed. There was no association between either polymorphism and disease susceptibility. Allele-2 of IL-1beta and allele-3 of the IL-1ra polymorphisms were associated with a favorable outcome (P=0.023 and P=0.030).