OBJECTIVE: Bipolar disorder is known to have strong genetic background and cellular immune activation. Based on the hypothesis that abnormalities of normal inhibitory control of T cell immunity can contribute to the pathophysiology of bipolar disorder, we investigated the relationship between the first exon at position +49(A/G) polymorphism of cytotoxic T lymphocyte antigen 4(CTLA4) gene and bipolar disorder. METHOD: Among the Korean patients diagnosed as bipolar disorder according to DSM-IV, 90 patients without serious medical illness, neurologic illness, hormonal disorder, or concomitant mental illness were selected. The normal control group consisted of 149 age-and sex-matched subjects without current or past history of autoimmune diseases or mental disorder. DNA was extracted from whole blood and the exon 1 region of CTLA-4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. RESULTS: There were no significant differences in genotype frequencies of G/G, G/A, and A/A between the patients with bipolar disorder and the control group(48.9% vs 46.3%, 44.4% vs 39.6%, and 6.7% vs 14.1%, respectively). There were no significant differences in allelic frequencies of G and A between the patients with bipolar disorder and the control group(71.1% vs 66.1%, and 28.9% vs 33.9%, respectively). CONCLUSION: This study did not show the association of exon 1 polymorphism of CTLA-4 gene with bipolar disorder.