Immunogenic regions in human TSH receptor responsible for autoimmune thyroid disease have been studied using synthetic TSH receptor-related peptides. Eight different peptides corresponding to segments of the extracellular domain of TSH receptor were synthesized. Immunoglobulin G (IgG) of patients with Graves' disease significantly bound to peptide #1 (32-56) compared with IgG of control subjects, and IgG of three of eight patients with Graves' disease showed increased binding to peptide #5 (309-337). In contrast, IgG of patients with Hashimoto's thyroiditis significantly bound to peptide #8 (333-359). The binding rates of Hashimoto's IgG to peptide #8 positively correlated with both MCHA and TGHA titers. These results suggest that heterogeneity of binding sites in TSH receptor for autoimmune thyroid disease may be responsible for pathophysiology of hyperthyroidism and hypothyroidism.