We have investigated the T-cell antigen receptor constant beta and alpha chain genes (TCR-C beta, -C alpha) and the immunoglobulin (Ig) heavy chain switch regions of patients with Graves' disease (GD) using restriction fragment length polymorphism (RFLP) analysis. No significant associations were found with RFLPs of either the TCR-C beta, -C alpha or Ig heavy chain switch region loci and GD. However, a significant association was found between the presence of anti-thyroglobulin (anti-Tg) antibodies in the serum of patients and the 10.0; 9.2 kb TCR-C beta genotype (P less than 0.02). Also, those patients with anti-Tg antibodies had an increased frequency of HLA-DR3 (P less than 0.025). These results suggest that genes residing in the TCR chain and major histocompatibility complex loci may be important in determining the immune response to thyroglobulin but not to the disease itself.