The effects of thyrotropin-releasing hormone (TRH) administration on electroconvulsive therapy (ECT)-induced prolactin (PRL) secretion and the duration of the seizure were studied in 14 depressed women. In a balanced order crossover design the patients were given 0.4 mg TRH or placebo intravenously 20 min before ECT during the first two sessions. In the third ECT session TRH was given just prior to ECT. ECT elicited the expected PRL response when given alone and when given 20 min after TRH when PRL plasma levels were high. During the coadministration design (third ECT session) PRL levels were raised not as a sum of the two stimuli but even significantly more. TRH failed to modify the duration of the seizure induced by ECT. Therefore, if TRH is involved in seizure modulation during ECT, our findings suggest a postictal rather than ictal role for TRH.