Abstract The purpose of the present paper was to investigate the relationship between the first exon at position +49 (A/G) polymorphism of the cytotoxic T lymphocyte antigen 4 (CTLA4) gene and bipolar disorder. Among the Korean patients diagnosed with bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders (4th edn; 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 peripheral blood using proteinase K; and the exon 1 region of the CTLA4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. There were no significant differences in genotype frequencies of CTLA4*G/G, CTLA4*G/A, and CTLA4*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 CTLA4*G and CTLA4*A between the patients with bipolar disorder and the control group (71.1% vs 66.1%; 28.9% vs 33.9%, respectively). In the present study an association was not found of exon 1 (+49) polymorphism of CTLA4 gene with bipolar disorder in the Korean population.