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Cytokine profiles have linked suicidal behavior to the immune system, suggesting a role for “neuroinflammation” in suicide. Classical inflammation of the CNS includes influx of leukocytes and increased permeability of the blood-brain barrier (BBB). Two prior studies of microglia in autopsy brains compared depressed suicides with psychiatrically normal nonsuicides, and only one included white matter (WM). To investigate microglial response in prefrontal WM related to suicide per se, we counted microglia from 11 suicides and 25 nonsuicides matched by age, sex, and psychiatric diagnosis. We classified Iba-1-immunoreactive (IR) cells based on shape, IR to CD68, and association with blood vessels to obtain stereologic estimates of densities of resting microglia, activated phagocytes, and vessel- associated cells. We found no effect of psychiatric diagnosis but two statistically significant effects of suicide: 1) The dorsal-ventral difference in activated microglial density was reversed such that, with suicide, the density was greater in ventral prefrontal WM than in dorsal prefrontal WM, whereas in the absence of suicide, the opposite was true; and 2) with suicide, there was a greater density of Iba-1- IR cells within or in contact with blood vessel walls in dorsal prefrontal WM. Neurological and psychiatric disorders have both been linked to immunological activity, but BBB permeability has been recognized only in classical neurological diseases. Increased densities in suicide of Iba-1-IR cells within or adjacent to vascular walls suggest that neuroinflammatory alterations in the BBB may be involved, possibly reflecting a mechanism whereby stress creates a suicidal state.