BACKGROUND Global and regional deficits in cerebral blood flow and glucose metabolism have been reported in major depression, but there is limited information on the effects of somatic treatment and clinical recovery on these abnormalities. METHODS We assessed cortical blood flow with the xenon 133 technique in depressed patients prior to a course of electroconvulsive therapy (ECT), 30 minutes before and 50 minutes after a single treatment, and during the week following ECT. Acute (preictal and postictal) effects of a single treatment also were studied in manic patients. RESULTS In the depressed and manic groups, larger blood flow reductions in the acute period, both globally and in particular patterns of brain regions, were associated with a superior clinical outcome following the treatment course. In depressed patients, similar patterns were observed for the blood flow changes over a full treatment course. Blood flow reductions in anterior cortical regions were strongly associated with a positive clinical response in both depression and mania. CONCLUSIONS The findings indicated that cerebral blood flow abnormalities in major depression were not reversed by successful treatment with ECT. Rather, particularly in responders, ECT resulted in additional perfusion reductions. The therapeutic properties of ECT are related to reduced functional brain activity in specific neural regions.