Neurotrophin 3 (NT-3) is a member of the neurotrophin gene family which supports the survival of specific neurons. NT-3 was shown to prevent the death of adult central noradrenergic neurons in vivo, a neuronal population which is associated with the pathophysiology of major depression. We quantitated CSF levels of NT-3 in elderly patients with major depression (DE) and compared them to patients with Alzheimer's disease (AD), and mentally healthy control subjects (CTR). CSF levels of NT-3 were markedly and significantly elevated in the DE group, as compared to either the AD or the CTR group (P < 0.01, and P < 0.001, respectively). In terms of diagnostic accuracy, measurement of NT-3 levels in DE resulted in 73.9% sensitivity, and 89.7% specificity. Increased CSF levels of NT-3 may indicate a disturbance of the central noradrenergic system in patients with DE. NT-3 may constitute a biochemical candidate marker for clinical diagnosis and for the evaluation of therapeutic strategies in DE.