Several reports have suggested a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder and schizophrenia. We have focused on the relationship between deleted mitochondrial DNA (mtDNA) and bipolar disorder. To investigate this relationship, we developed a methodology for quantification of the common 4977-bp deletion of mtDNA based on real-time polymerase chain reaction with SYBR Green. In this study, we assessed accumulation of the common deletion in postmortem frontal cortex from 147 individuals (48 controls, 49 patients with bipolar disorder, 50 patients with schizophrenia). We demonstrated age-dependent accumulation of the common deletion of mtDNA (p=1.09E-10). Females showed significantly higher accumulation of the deletion than did males (p=0.002). There was no significant association between accumulation and the two studied major mental disorders in the frontal cortex (p>0.2). However, there was no statistically significant correlation between the common deletion and aging in female patients with bipolar disorder (p=0.133), and no significant sex difference in patients with bipolar disorder (p=0.509). These results indicate that aging and sex have effect on accumulation of the common deletion of mtDNA in the prefrontal cortex depending on the diagnosis.