Hormones of the hypothalamo-pituitary-adrenocortical (HPA-) axis are considered to be of physiological and clinical relevance in regulating spontaneous growth hormone (GH) secretion. To further investigate interdependencies between both systems, we studied the effects of adrenocorticotropin [ACTH(1–24)] and human corticotropin-releasing hormone (h-CRH) upon spontaneous GH secretion in 10 male volunteers. Administration of 1 µg ACTH (1–24), 10 µg h-CRH or saline (control: CTL) every hour from 9.00 to 6.00 p.m. resulted in significant differences of cortisol secretion during the entire observation period (8.00 a.m.-3.00 a.m.) between the three groups (p < 0.001, Friedman two-way ANOVA). Mean area under the time course curve (AUC) values (± SEM) for cortisol expressed as ng × 1,000 × min/ml showed also significant differences between the three treatments from 8.00 a.m. to 3.00 a.m.: CTL 64.0 ± 6.4, ACTH(1–24) 178.5 ± 9.4 (p < 0.01, Wilcoxon test), h-CRH 88.5 ± 5.6 (p < 0.01). The main portion of cortisol was released during daytime from 8.00 a.m. to 11.00 p.m., where the most significant differences in the AUC values emerged: CTL 59.6 ± 5.8, ACTH(1–24) 171.5 ± 8.8 (p < 0.01, Wilcoxon test), h-CRH 80.2 ± 5.1 (p < 0.01). With regard to GH secretion, significant differences became obvious between the three treatments during daytime from 8.00 a.m. to 11.00 p.m. and the sleep-related period from 11.00 p.m. to 3.00 a.m. (p < 0.01 and p < 0.02, Friedman two-way ANOVA). The pulse frequency also differed significantly between the treatments during daytime (p < 0.02). Mean AUC values (± SEM) expressed as ng × min/ml for GH from 8.00 a.m. to 11.00 p.m. were: CTL 2,507 ± 614, ACTH(1–24) 3,419 ± 801 (p < 0.02, Wilcoxon test). AUC values for GH from 11.00 p.m. to 3.00 a.m. were: CTL 2,033 ± 368, ACTH(1–24) 1,136 ± 147 (p < 0.02, Wilcoxon test). Also, the number of GH secretory pulses is increased by stimulation with AOΗ(1–24). Stimulation with h-CRH in the same experimental schedule resulted in allusively similar effects, which were less pronounced. While prolonged exposure of somatotrophs to glucocorticoids results in a reduction of GH secretion, short-term exposition to glucocorticoids as resulting from our present stimulation with ACTH(1–24) enhances the amount of GH released. From our current data, we conclude that HPA hormones modulate the spontaneous GH release pattern. This has implications for the interpretation of neuroen-docrine studies in patients with depression, where exaggerated HPA activity often concurs with elevated GH secretion during daytime and decreased GH surges during sleep or following pharmacological stimuli.