Clinical, neuropsychological, and electroencephalogram (EEG) data from 150 ECT-treated patients with affective disorders were analyzed to bear upon current hypotheses about neurophysiological mechanisms of action of electroconvulsive therapy (ECT). Comparisons of responders and nonresponders revealed little or no evidence to support kindling, sensitization, diencephalic stimulation, or anticonvulsant theories. Neuropsychological test data supported right hemispheric dysfunctions in affective illness which resolved more in ECT responders than in nonresponders. There were more impairments in dominant and bilateral hemispheric functions after successful than after unsuccessful ECT. The amount of EEG slowing and paroxysmal activity was not related to therapeutic response. Transient left-sided EEG slowing was associated with positive ECT response whereas right-sided EEG changes were not. The data support the hypothesis that in patients with affective disorders, ECT restores hemispheric equilibrium with enhancement of right brain functions and dampening of the left.