It has been suggested that growth hormone (GH)-releasing hormone (GHRH) stimulates the surge in GH and enhances slow-wave sleep (SWS), two phenomena that characterize the beginning of nocturnal sleep. However, in human studies the effects of systemic GHRH administration on sleep were not consistent. This may reflect the differential influence of administration procedures being episodic in one of the above studies, but either a continuous infusion or a single bolus in the others. The present study in healthy volunteers compared changes in nocturnal sleep following 200 μg GHRH administered iv either episodically (4 boluses of 50 μg each at 2200, 2300, 2400, and 0100 h) or as a continuous infusion (57 μg/h between 2130 and 0100 h). Time spent in stage 4 of SWS on nights of episodic GHRH administration significantly exceeded that on nights of continuous GHRH administration (P < 0.01). Compared with a placebo condition, episodic administration of GHRH enhanced SWS (P < 0.01) and rapid eye movement (REM) sleep (P < 0.05) and diminished time spent in wakefulness and sleep stage 1 (P < 0.05). Effects of continuous GHRH infusion on sleep generally remained insignificant compared with placebo. Plasma GH concentrations were enhanced during both conditions of GHRH administration (P < 0.01), with the increase following episodic administration slightly exceeding that during continuous infusion (P < 0.05). The results support a greater physiological efficacy of episodic GHRH stimulation in promoting sleep.