Combined gas chromatographic mass spectrometric methods can be employed to assess total body turnover of norepinephrine (sum NE) and dopamine (sum DA) in human subjects and rats, and to further assess and determine the role of peripheral and central catecholamines and other biogenic amines in mental illness. We have used this method in a number of such experiments. (I) We continue to gather data that support that there is a tendency for sum NE to be elevated in major depression, and have also observed a positive correlation between urinary-free cortisol, urinary NE and vanillinemandelic acid (VMA), a major metabolite of NE in the periphery in humans. (2) Total body NE and DA turnover was assessed in both hyperactive children and adults after several pharmacological manipulations. The results indicated a correlation between therapeutic benefits and changes in both sum NE and DA irrespective of the direction of change. (3) In depressed patients, total NE turnover was found to be reduced, while DA turnover was found to be low in schizophrenic patients. (4) The effects of four commonly used antidepressant treatments (chronic zimelidine, desipramine, electroconvulsion, and lithium) on rat peripheral and central catecholamines were evaluated. A good correlation between the effects of these drugs and sum NE and sum DA in humans and rats was observed. We suggest that because of this correlation, changes in rat brain amines probably resemble those changes induced by these treatments in the human brain; therefore, a similar correlation may be observable in humans. (5) We are currently attempting to reproduce our initial study on DA and NE turnover in schizophrenia, and hope to also include patients with tardive dyskinesia. (6) The above procedures were employed in the evaluation of central and peripheral production of catecholamines in patients suffering from Norrie Disease. (7) The procedures that were developed are also being emploYed to study DA and NE turnover in cocaine addicts during withdrawal.