Genetic factors for panic disorder have been consistently observed in family and twin studies. Regulators of G-protein signaling (RGS) is a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors such as dopamine and serotonin receptors. RGS2, one of the RGS families, has been suggested to plays a role in anxiety and/or aggressive behavior. Polymorphisms in the RGS2 gene were recently associated with panic disorder, trait anxiety, suicidal behavior, and generalized anxiety disorder. From these findings, we tried to replicate an association between panic disorder and genetic variations of the RGS2 using a case-control study of 186 patients with panic disorder and 380 controls in Japanese. We genotyped five common single nucleotide polymorphisms (SNPs) by the PCR-RFLP method and the TaqMan Assays. Neither genotype distribution nor allele frequency for five SNPs was significant different between the panic disorder and control groups. We found a relative tight LD block in the 5'- flanking region of RGS2 gene. One of the common haplotypes, AC of rs2746071 and rs2746072, has shown a nominally significant association with panic disorder (p=0.027). This significance, however, did not remain after correction for multiple testing. These findings suggest that RGS2 may not be genetically involved in the biological susceptibility to panic disorder in Japanese.