Twenty-eight unrelated hemophilia A patients, seven of them with anti-factor VIII antibodies were typed for HLA-A, B, C antigens and 25 of them for HLA-DR. The results show a significant difference in HLA-DR4 frequency between hemophiliacs with antibodies who lack this antigen and hemophiliacs without antibodies, in whom HLA-DR4 is increased as compared to a healthy control series. This data suggests that DR4 may be associated with a factor preventing anti-factor VIII immunization.