Thyrotropin (TSH), thyroxin (T4), triiodothyronine (T3), free T3 (fT3), cortisol, prolactin, and human growth hormone (HGH) were measured every 2 hr during a night of sleep, the following day, and a night of sleep deprivation (SD) in 14 patients with major depressive disorder. In subgroups fT4 (n = 5), reverse T3 (rT3), and luteinizing hormone (LH) (n = 6) were also investigated. Significant increases in TSH, T4, fT4, T3, fT3, rT3, and cortisol and decreases in prolactin levels occurred during the night of SD, compared to the pattern during the night of sleep. The pre-SD T4 and T3 levels of the responders to SD were already higher than in the nonresponders, and increased less during SD. The cortisol and HGH concentrations of the responders rose higher during SD than those of the nonresponders. Changes in TSH and prolactin were not correlated to clinical response. Analysis of possible neurochemical mechanisms underlying this "pattern" of changes in different endocrine profiles suggests that enhanced noradrenergic activity might play a role in the changes in TSH, cortisol, thyroid hormones, and possibly HGH secretion during SD, and increased dopaminergic tone probably induced the decline in prolactin levels. Additional effects of the serotonergic system cannot be excluded at present. In conclusion, the data suggest that enhanced noradrenergic activity of the locus coeruleus stimulates alpha and/or beta adrenergic receptors in depressed patients during SD. This mechanism could well be involved in the antidepressant effect of this therapy.