We investigated the acute and lasting effects of electroconvulsive therapy (ECT) on the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in patients with depression. The TRH stimulation test was conducted (1) under basal conditions, after a first ECT, and at the end of a therapeutic course of 7 ECTs in 20 inpatients with depression; (2) before the initiation of antidepressant therapy and after the therapeutic response in 16 other inpatients with depression who responded to antidepressant drug treatment; and (3) in 20 healthy control subjects. Baseline TSH levels were lower in patients with depression, especially in those with more severe depression who were considered appropriate for ECT. Before the treatment, TSH response to TRH did not differ between the patients with depression and controls; however, more blunted TSH responses to TRH were observed in these patients compared with the controls. TSH response to TRH changed neither with one ECT nor throughout consecutive ECT sessions in patients with depression. Drug treatment also was found to have no impact on this response. These findings suggest that the therapeutic action of ECT in depression is not directly related to its effects on the hypothalamic-pituitary-thyroid axis. However, possible delayed effects of ECT on the HPT axis function should not be overlooked.