To evaluate the frequency of anti-thyroid antibodies in a group of patients with scleroderma (SSc) and to analyze their genetic association with the HLA class II antigens.Anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) antibodies were measured by hemagglutination techniques. Thyroid function was evaluated by determining the levels of FT3, FT4 and TSH. HLA-DR typing was carried out using a standard complement-dependent microlymphocytotoxicity test.The proportions of patients with anti-TG and anti-TPO antibodies were 12% (10/85) and 19% (16/85) respectively. Two patients with anti-thyroid antibodies had overt hypothyroidism and shared the HLA-DR3 allele. The SSc subjects with anti-TPO antibodies showed a higher frequency of the HLA-DR15 allele than the patients without these antibodies.A considerable number of patients with scleroderma have antibodies to thyroid antigens without exhibiting any alterations of their thyroid function. HLA-DR15 is an immunogenic marker for the formation of antibodies against microsomal thyroid peroxidase.