Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system. Autoantibodies are though to participate in the pathogenesis. Previous reports on the role of immunoglobulin (Ig) variable gene segments in MS are contradictory. Here, by using a highly polymorphic variable number tandem repeat (VNTR) marker located in the centre of the IgH chain locus, we demonstrate a lack of linkage and association with MS in 34 multiplex families and 113 sporadic MS patients in Sweden. Stratification for the presence or absence of the MS-associated HLA-Dw2 haplotype did not influence the negative outcome. We conclude that the IgH chain genes are unlikely to play a role in genetic susceptibility to MS in the Swedish population.