Objective: Pediatric bipolar disorder (PBD) is a major public health concern; however, little is known about the cellular and genetic factors that are involved in the pathophysiology of this illness. The observed structural abnormality in the brains of patients with mood disorders has been related to abnormal brain-derived neurotrophic factor (BDNF) function, suggesting an important role for BDNF in these disorders. Method: We determined the gene expression of BDNF in lymphocytes obtained from 26 PBD subjects during a drug-free baseline period and during the eighth week of treatment (n = 19) and from 21 medication-free normal control subjects. We also determined the protein levels of BDNF in platelets of patients with PBD and normal control subjects. Subjects were diagnosed according to DSM-IV diagnostic criteria using the Washington University at St. Louis Schedule for Affective Disorders and Schizophrenia. Results: The mRNA levels of BDNF in lymphocytes of PBD subjects were significantly decreased compared with those of normal control subjects and were significantly higher in 19 subjects after 8 weeks of treatment than the pretreatment drug-free baseline levels and similar to those of normal controls. Similarly, protein levels of BDNF were decreased in platelets of patients with PBD. Conclusions: These studies suggest that BDNF levels may be a potential biomarker for PBD. BDNF levels may also serve as a potential treatment predictor and prognostic indicator in PBD. ©2008 by the American Academy of Child and Adolescent Psychiatry.