Serological abnormalities and HLA haplotypes were studied in a Japanese family of two patients with Sjögren's syndrome (SS) associated with other autoimmune diseases. In contrast to the reports in the U.S.A. and Europe, we found a significant excess of HLA-DRw53 antigen in the family members. Two family members, mother and niece of the probands, had suffered from other connective tissue diseases. Although none of the siblings of probands had manifestations of connective tissue diseases, two siblings had several autoantibodies. No consistent segregation, however, was found between the HLA haplotypes and the serological abnormalities in the relatives. Therefore, HLA alone can not explain the familial clustering of autoimmune diseases including SS and of autoantibodies.