Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticity may be fundamentally involved in the illness.