Clinical and basic research findings implicate a role for brain norepinephrine in the pathophysiology of psychiatric disorders that can lead to suicide. However, the precise biological abnormality of neurons that produce norepinephrine in the brain in these disorders has not been elucidated. We have studied the biochemistry of the locus coeruleus (LC), the principal source of brain norepinephrine, from suicide victims and from age-matched, natural or accidental death control subjects. Levels of tyrosine hydroxylase (rate-limiting enzyme in norepinephrine biosynthesis) and amounts of binding to a2 adrenoceptors (norepinephrine receptors) are elevated in the LC of suicide victims as compared to control subjects. These biological abnormalities in the LC from suicide victims are very similar to biochemical changes observed in the rat LC following repeated exposure to environmental stimuli that activate the LC or to treatment with pharmacological agents that deplete brain norepinephrine. It is hypothesized that persons who commit suicide have experienced chronic activation of the LC, resulting in depletion of synaptic norepinephrine and compensatory changes in concentrations of noradrenergic proteins.