EEG, pulse rate, respiration and eye movement were polygraphically recorded throughout the night in 10 normal adult male subjects. Blood was collected every 20 min throughout the night by means of an indwelling venous catheter without disturbing the natural course of sleep. Human growth hormone (HGH) and blood sugar were measured in these plasma samples. Depth of sleep was classified into 5 stages by EEG. A marked elevation of plasma HGH was constantly observed coincident with the onset of sleep. Following the initial large HGH peak, additional peaks of HGH, with a decrease in the size of subsequent peaks, were observed. Shifting the time of the onset of sleep by 3 hr before or after the usual bedtime did not change the elevation of plasma HGH coincident with the onset of sleep. When a state of full wakefulness was maintained at night, plasma HGH did not rise. The secretion of plasma HGH was inhibited during paradoxical sleep. It is concluded that nocturnal sleep is a potent stimulator for the secretion of growth hormone, and that the secretion pattern of HGH is closely correlated with the depth and the course of sleep. We propose a hypothesis that neocortical activation inhibits the secretion of HGH, and slow wave sleep induces the secretion of growth hormone releasing factor in the hypothalamus.