Various peptides including corticotropin-releasing hormone (CRH) exert selective effects on sleep structure and noctural secretions of cortisol and growth hormone (GH). In animal studies analeptic effects and sleep disturbances after thyrotropin-releasing hormone (TRH) administration have been observed; studies of endocrine function in depressed patients suggest a pathological activity of CRH and TRH as compared with that in healthy volunteers. As the role of TRH in the regulation of the sleep endocrine pattern in humans has not yet been clarified, we performed a study to examine the effects of pulsatile administration of TRH on the sleep EEG pattern and the nocturnal secretions of cortisol and GH in 7 healthy male subjects. The sleep EEG was recorded from 23.00 to 07.00 h, and blood samples were collected every 20 min from 20.00 to 07.00 h for the analysis of GH and cortisol concentrations during intravenous administration of placebo or 4 x 50 microgram TRH at 22.00, 23.00, 24. 00, and 01.00 h. In contrast to the well-known effects of CRH on the sleep endocrine pattern, TRH exerts only a weak effect on the sleep EEG which is reflected in a slight decrease in sleep efficiency associated with a trend to wakefulness during the night. Furthermore, after TRH administration, the cortisol rise appeared earlier, and a nonsignificant tendency to an increased secretion of cortisol during the first half of the night was found. The GH secretion did not differ significantly after application of TRH or placebo. The activating, albeit weak, effect of TRH on the sleep EEG and nocturnal cortisol secretion in healthy volunteers confirms and adds to the results previously observed in animals. On the basis of these findings, we surmise that TRH may contribute to the disturbed sleep continuity seen in depressed patients, probably acting as a cofactor of CRH in a synergistic manner.