Background: Neurotrophins mediate diverse biological responses, including maintenance and growth of neurons and synaptic plasticity in adult brain. This study examined whether suicide brain is associated with changes in the expression of neurotrophins. Methods: Messenger ribonucleic acid (mRNA) levels of nerve growth factor (NGF), neurotrophin (NT)-3, NT-4/5, and of cyclophilin and neuron-specific enolase (NSE) were measured by quantitative reverse transcriptase polymerase chain reaction, whereas protein levels of neurotrophins were determined by enzyme-linked immunosorbent assay, in prefrontal cortex (PFC) and hippocampus from 28 suicide victims and 21 control subjects. Results: In hippocampus of suicide subjects compared with control subjects mRNA levels of NGF (p < .001), NT-3 (p < .001), and NT-4/5 (p < .001) were decreased, whether or not they were expressed as a ratio to cyclophilin or NSE. This was accompanied by a decrease in their respective protein levels (NGF [p < .001], NT-3 [p < .001], and NT-4/5 [p < .001]). In PFC, however, mRNA (p = .001) and protein (p < .001) levels of NT-4/5 and only protein level of NGF (p < .001) were decreased; NT-3 levels were unchanged. Conclusions: Given the role of neurotrophins in synaptic plasticity and maintenance of adult neurons, our findings of altered expression of neurotrophins in postmortem brain of suicide victims suggest that these molecules might play a vital role in the pathophysiology of suicide. © 2005 Society of Biological Psychiatry.