Mutations in mitochondrial DNA (mtDNA) have been implicated in the pathophysiology of affective disorders. To examine possible pathophysiological significance of mtDNA deletions in bipolar disorder, the concentration of the 4977-base-pair deletion in mtDNA in the autopsied brains of 7 patients with bipolar disorder, 9 suicide victims, and 9 controls was examined using a quantitative polymerase chain reaction method. The ratio of deleted to wild-type mtDNA in cerebral cortex was significantly higher in patients with bipolar disorder [0.23 +/- 0.18 (mean +/- SD)%] compared with that in age-matched controls (0.06 +/- 0.07%, p < 0.05). This result supports a hypothesis that mtDNA deletions may play a role in the pathophysiology of bipolar disorder.