An emerging body of evidence points to a role for neurotrophins in the pathophysiology of Bipolar Disorder (BD). Serum BDNF levels were found to be decreased during both manic and depressive episodes, with no difference from controls during remission, and serum neurotrophin-3 (NT-3) levels in manic and depressive episodes were found elevated in comparison with euthymic patients and controls. In order to investigate this apparently inverse relationship, we assessed the correlation between serum BDNF and NT-3 levels in a sample of outpatients with BD. There was a negative correlation between serum BDNF and NT-3 levels (r=-0.48, p=0.001). This adds to the notion that an increase in NT-3 levels occurs in tandem with a decrease in BDNF levels and that this may represent a compensatory response to the decrease in BDNF reported in mood episodes.