To clarify the role of catechol-O-methyltransferase (COMT) polymorphism in panic disorder (PD), we investigated a large group of Korean PD patients (N=178) and controls (N=182) using a case-control study. We also assessed the response to paroxetine treatment and other clinical variables in the PD patients. The increase in the COMT L allele was not statistically significant in PD (p=0.104). However, compared with the sum of the other genotypes, the frequency of the L/L genotype was significantly higher in PD (p=0.042). The odd ratios (ORs) also indicated a significant effect of the homozygosity for the COMT L allele on an increased risk for PD (OR=2.38; 95% CI 1.03-5.51). In addition, patients with L/L genotype had higher trait-anxiety levels (p=0.030) and poorer treatment response to paroxetine than those with other genotypes (p=0.002). Our results suggest that the COMT L/L genotype is associated with PD and the genetic variant of the COMT enzyme may be related to the clinical severity and treatment response to paroxetine in PD.