Studies in normal human subjects and animals suggest that the neuropeptide growth hormone-releasing hormone (GHRH) is a common regulator of the sleep EEG and nocturnal hormone secretion. In healthy volunteers GHRH prompts an increase in the amount of slow wave sleep (SWS) and in growth hormone (GH) secretion and blunting of cortisol release. Inhibition of GHRH may contribute to sleep-endocrine aberrances during depression. We tested the effects of pulsatile application of 4 x 50 micrograms GHRH on the sleep EEG and simultaneously investigated nocturnal hormone secretion in 10 inpatients (four females, six males) with the acute episode of major depression. In contrast to the effects of placebo, GH secretion increased distinctly and rapid-eye-movement (REM) density decreased during the second half of night. No other significant changes in sleep-endocrine activity, including SWS, cortisol and ACTH secretion, could be observed. We assume that hypothalamic-pituitary-adrenocortical system activity and slow wave sleep are inert to the influence of GHRH during acute depression. Cortisol and ACTH remained unchanged even in a subsample of five younger (aged 19-28 years) patients. This observation is in contrast to our recent finding that cortisol secretion is blunted in young normal volunteers after GHRH. But on the other hand, GHRH is capable of stimulating GH and inducing a decrease in REM density in these subjects.