Genetic factors, such as the genes involved in the serotonin pathway, probably play an important role in the pathogenesis of bipolar disorder, and serotonin type 2A (5-HT2A) receptor gene promoter polymorphism -1438A/G has been reported. This study investigated the association between -1438A/G polymorphism of 5-HT2A receptor gene promoter and bipolar disorder in a Korean population. Using the polymerase chain reaction, -1438A/G polymorphism typed in 142 patients with bipolar disorder and in 148 normal control subjects. Differences in genotype distributions and allele frequencies of -1438A/G between patients with bipolar disorder and normal control subjects were tested for significance using the chi-squared test. There were significant differences in genotype distributions [chi2 = 9.697, degrees of freedom (df) = 2, P = 0.008] and allele frequencies (chi2 = 7.284, df = 1, P = 0.007) of -1438A/G between patients with bipolar disorder and normal control subjects. Although further studies are necessary, these results in a Korean population suggest that -1438A/G polymorphism of 5-HT2A receptor gene promoter may be causally related to the development of bipolar disorder.