BACKGROUND: Panic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population. METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared. RESULTS: We found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P=0.031, OR=1.81, 95% CI=1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P=0.042, genotype P=0.0034; haplotype C-T-T-A, permutation P=0.028). CONCLUSION: Our results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions.