In the frontal cortex of suicide victims, the density of I2-imidazoline receptors labeled by [3H]idazoxan was lower (40%) than that in healthy subjects. In the same brains, the immunoreactivity of a 29/30 kDa imidazoline receptor protein was also found to be significantly decreased (19%) and it showed a positive correlation with the density of I2-imidazoline receptors. Also in the same brains, the density of alpha 2-adrenoceptor antagonist binding sites labeled by [3H]RX821002 (2-methoxy idazoxan) was found to be unchanged. The density of brain I2-imidazoline receptors, correlated with aging in control subjects but not in suicides. The density of brain MAO-B sites labeled by [3H]Ro 19-6327 (lazabemide) in suicides was no different to that in age-matched controls. As expected the density of brain MAO-B sites in suicides showed a positive correlation with age, but it did not correlate with the density of I2-imidazoline receptors in the same brains. The data indicate that the I2-imidazoline receptors labeled by [3H]idazoxan in the brain of suicides is related to a 29/30 kDa imidazoline receptor protein identified by immunoblot analysis. The data also indicate that the brain I2-imidazoline receptor cannot be identified with the MAO-B isoenzyme. The decreased density of I2-imidazoline receptors in the brain of suicide victims might play a role in the pathogenesis of major depression.