• In order to study a possible hereditary factor leading to multiple sclerosis (MS) susceptibility, histocompatibility (HL-A) types were studied in families where two or more first-degree relatives had MS. Neither the inheritance of a particular parental HL-A chromosome, nor the occurrence of any specific HL-A antigens, could be shown to be necessary or sufficient for the development of MS in family members. The distribution of HL-A chromosomes was essentially the same for affected and unaffected family members. An excess of the 3,7 haplotype and W21 antigen was demonstrated, both in affected patients and in unaffected family members, in equal proportions. We conclude that the HL-A chromosome has no direct causal relationship to MS susceptibility, although it may be indirectly associated by population stratification, maternal factors, or some other mechanism.