A significant portion of the total daily growth hormone (GH) secretion is associated with deep non-REM sleep (NREMS). GH secretion is stimulated by the hypothalamic neurohormone, GH-releasing hormone (GHRH). Exogenous GHRH promotes NREMS in various species. Suppression of endogenous GHRH (competitive antagonist, antibodies, somatostatinergic stimulation, high doses of GH or insulin-like growth factor) results in simultaneous inhibition of NREMS. Mutant and transgenic animals with a defect in GHRHergic activity display permanently reduced NREMS which cannot be reversed by means of GH supplementation. GHRH contents and mRNA levels in the hypothalamus correlate with sleep-wake activity during the diurnal cycle and sleep deprivation and recovery sleep. Stimulation of NREMS by GHRH is a hypothalamic action. GABAergic neurons in the anterior hypothalamus/preoptic region are candidates for mediating promotion of NREMS by GHRH. In contrast to NREMS, stimulation of REMS by GHRH is mediated by GH. Simultaneous stimulation of NREMS and GH secretion by GHRH may promote adjustment of tissue anabolism to sleep.