The mechanism of action of electroconvulsive therapy (ECT) in treating major depression is unknown. We studied two candidate mechanisms through inhibiting simultaneously the synthesis of noradrenaline and serotonin in patients immediately after successful treatment with ECT using a randomised, placebo-controlled, double-blind crossover design. There were no significant changes in depression scores under any experimental conditions, or between the amine-depleted and placebo groups despite reductions of 61% in serum homovanillic acid, 47% in 3-methoxy-4-hydroxyenylethyleneglycol, and 89% in serum tryptophan. Catecholamine and serotonin availability may not be necessary for maintaining the initial antidepressant response to ECT.