It has been suggested that personality traits are heritable. The polymorphic cytochrome P450 (CYP) 2C19 metabolizes sex hormones and 5-hydroxytryptamine, which are involved in multiple brain functions. In the present study, the relationship between the CYP2C19 polymorphism and personality traits was examined in 487 Japanese healthy volunteers. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the two mutated alleles causing absent CYP2C19 activity were identified by a PCR-RFLP method. In females, the scores of reward dependence (p=0.026), cooperativeness (p=0.001), and self-transcendence (ST) (p=0.049) were significantly lower in poor metabolizers (PMs) than in extensive metabolizers (EMs). In males, none of the seven TCI dimensions was significantly different between EMs and PMs. The present study thus suggests that the CYP2C19 polymorphism affects personality traits of Japanese females.