Converging lines of evidence implicate the neurotrophin brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depression. Recent studies have begun to explore the relationship between serum BDNF and depression. We conducted meta-analyses of 11 studies examining differences in serum BDNF content between depressed and nondepressed subjects (N = 748), and eight studies comparing pre- and post-antidepressant treatment serum BDNF content (N = 220). The meta-analysis revealed strong evidence that BDNF levels were lower in depressed subjects than healthy control subjects (p < 6.8 x 10(-8)). Similarly, the second meta-analysis found significantly higher BDNF levels after antidepressant treatment (p = .003). There was no evidence of publication bias in the first (p = .376) or second (p = .571) meta-analysis and no evidence that either meta-analysis was unduly influenced by any one study. These findings provide strong evidence to suggest that serum BDNF levels are abnormally low in patients suffering from major depressive disorder and that the BDNF levels are elevated following a course of antidepressant treatment. Although the relationship of our findings to pathophysiology of depression and the mechanism of drug action remains to be determined, the measure may have potential use as a biomarker for psychiatric disorders or as a predictor of antidepressant efficacy.