The effects of an intravenous application of melatonin upon eye movements and muscular tonus were examined in acute decerebrate cats in order to elucidate whether melatonin can be beneficial as a therapeutic agent for treating sleep disturbance. The results were compared with those produced by an intravenous application of diazepam, one of the benzodiazepines, and from a microinjection of carbachol, a cholinergic agent resistant to cholinesterase, into the pontine reticular formation. The application of melatonin did not produce either changes in muscle tone or eye movements in cats; the decerebration was made at the precollicular-postmammillary level (mesencephalic cats). However, it did produce rapid eye movements (REM) with muscular atonia in the cats; the decerebration was performed at the precollicular-preoptic chiasma level (hypothalamic cats). In the latter preparation, the suprachiasmatic nucleus (SCN) was preserved. Although an application of diazepam abolished muscle tone, it did not change eye movements in either mesencephalic or hypothalamic cats. An intrapontine carbachol injection resulted in muscular atonia associated with REM in the mesencephalic cats. These results suggest that the melatonin application influences SCN neurons, which, in turn, trigger a REM sleep-generating system in the brainstem. However, muscle tone suppression induced by the diazepam application may not be a result of the activation of the brainstem REM-sleep generating system. We expect that melatonin has a potential to be a beneficial and safe therapeutic agent for treating sleep disturbances.