Multiple sclerosis (MS) has been associated with the human leukocyte antigen DR15 allele in Caucasians of North and Central European origin. However, the relative effect of the DR15 homozygous and the DR15 heterozygous genotypes on the disease susceptibility is unclear. Based upon results from three North European studies we have examined this by meta-analysis. Our results suggested that the effect of the DRB1*1501,DQA1*0102,DQB1*0602 haplotype on the susceptibility to MS is additive, perhaps reflecting that development of the disease is facilitated by a high density surface expression of the antigen presenting molecules encoded by this haplotype. Possible implications of our finding to future studies of the genetic background of MS is discussed.