Previous studies of multiple sclerosis patients showed the existence of a positive association between multiple sclerosis and HLA--A3 and --B7, as well as a negative association with B12. These observations have been confirmed. In addition, a more marked association has been observed with two recently identified B-cell antigens, DRw2 and DRw3, closely related to the HLA--D locus. The presence of cold lymphocytotoxic antibodies was found to bear no relationship with those two specificities. These results suggest that two genes of the HLA--DR region may play a role in the pathogenesis of multiple sclerosis.