The brain-derived neurotrophic factor (BDNF) gene is a candidate gene for influencing the clinical response to treatment with antidepressants. The purpose of this study was to determine the relationship between the Val66Met polymorphism in the BNDF gene and the response to citalopram in a Korean population with major depressive disorder (MDD). Citalopram was administered for 8 weeks to the 83 patients who completed this study. We found that the genotype, allele, and allele-carrier distributions for the Val66Met polymorphism differed significantly between responders (Rp) and nonresponders (Non-Rp). The frequency of M-allele carriers (VM+MM) was higher in Rp than in Non-Rp (chi(2)=8.926, p=0.003, OR=4.375, 95%CI=1.609-11.892), as was the M-allele frequency (chi(2)=6.879, p=0.009, OR=2.500, 95%CI=1.249-5.005). There were also significant differences in the core (p=0.012) and activity (p=0.008) scores. Patients carrying the M-allele had a lower score. Also, patients carrying the M-allele tended to have lower psychic anxiety (p=0.072). The percentage change in the total HAM-D score was higher for M-allele carriers (VM+MM allele) than for noncarriers (p=0.034) after 8 weeks of medication. We found that the genotype, allele, and allele-carrier distributions did not differ significantly between MDD patients and normal controls. These results suggest that the Val66Met polymorphism of BDNF is associated with citalopram efficacy, with M-allele carriers responding better to citalopram treatment. Moreover, the Val66Met polymorphism was correlated with improvements in core, activity, and psychic anxiety symptoms.