The objective of this study was to examine the polymorphism in the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene and its relationship with autoimmune thyroid disease in Koreans. Polymorphism in the promoter and exon 1 of CTLA-4, clinical symptoms of disease and thyrotropin receptor antibody (TSHRAb) characteristics were analyzed. Polymorphism was detected using restriction fragment length polymorphism and polymerase chain reaction amplification of genomic DNA. All subjects were Korean (97 Graves' disease, 110 Hashimoto's thyroiditis, and 199 normal controls). Graves' patients had significantly more G allele in exon 1 and C allele in the promoter than controls. When the exon 1 genotype was GG, the frequency of CC genotype in the promoter was higher. Allele frequencies in CTLA-4 did not differ from controls in patients with Hashimoto's thyroiditis. In Graves' patients, there were significant differences between genotypic groups in serum triiodothyronine (T3) levels and the presence of ophthalmopathy. However, TSHRAbs and other clinical characteristics were not significantly different. In conclusion, the CTLA-4 G allele in exon 1 and C allele in the promoter may confer genetic susceptibility to Graves' disease in Koreans. These two polymorphisms are additional and dependent genetic risk markers that help to characterize risk alleles within CTLA-4 gene.