The effects of chronic excess of growth hormone (GH) on sleep-wake activity was determined in giant transgenic mice, in which the methallotionein-1 promoter stimulates the expression of rat GH (MT-rGH mice), and in their normal littermates. In the Mt-rGH mice, the time spent in spontaneous NREMS was enhanced moderately, and rapid eye movement sleep (REMS) time increased greatly during the light period. After a 12-h sleep deprivation, the MT-rGH mice continued to sleep more than the normal mice but there were no differences in the increments in non-rapid eye movement sleep (NREMS), REMS, and EEG slow wave activity (SWA) during NREMS between the two groups. Injection of the somatostatin analog, octreotide, elicited a prompt sleep suppression followed by increases in SWA during NREMS in normal mice. These changes were attenuated in the MT-rGH mice. The decreased responsiveness to octreotide is explained by a chronic suppression of hypothalamic GHRH in the MT-rGH mice. Enhancements in spontaneous REMS are attributed to the REMS-promoting activity of GH. The increases in spontaneous NREMS are, however, not consistent with our current understanding of the role of somatotropic hormones in sleep regulation. Metabolic, neurotransmitter or hormonal changes associated with chronic GH excess may indirectly influence sleep.