We scanned for all genetic variants in functionally important regions of the tumor necrosis factor receptor 1 gene (TNF-R1) in 100 to 111 MS patients from Olmsted County, MN, and analyzed selected variants for an association with disease course and severity. Ten genetic variants were uncovered. Only one variant, a silent substitution, was found in coding sequence. One intronic variant may generate a novel splice-junction sequence. We did not find an association between either this intronic variant or another common promoter variant and the course or severity of MS.