In 13 patients fulfilling DSM-III-R criteria for a major depressive episode, hormone serum levels were measured at 8 AM on the day before and on the first and second days after partial sleep deprivation (PSD) late in the night during a 4-week course of therapy with amitriptyline in combination with 6 PSDs. Prolactin, human growth hormone (HGH) and total corticoids were not influenced by PSD. In contrast, T3 and thyrotropine (TSH) were elevated significantly on the 1st day after PSD throughout the series, but T4 less regularly. Although TSH reverted regularly to baseline values on the 2nd day after PSD, i.e. after a full night's sleep, T3 remained elevated. The hormones under discussion do not predict the therapeutic PSD effect. Nor can any correlation be determined between endocrine and clinical changes on the 1st or 2nd day after PSD. In connection with findings from sleep deprivation research in animals and in healthy subjects, the results suggest that thyroid changes under PSD may be nonspecific and unrelated to antidepressive PSD effects.