The state of vigilance is closely interwoven by the nutritional state. However, taking into consideration the evolutionary aspects of the neuroendocrine control system in higher animals may provide a possible explanation. A neurohumoral regulatory system of sleep may have evolved from the basic circadian and/or ultradian rest-activity mechanism in parallel with the development of sleep, which represents a later acquired function in higher animals. The evolution of sleep has differentiated the sleep-like state in lower vertebrates into slow-wave sleep and paradoxical sleep in homeotherms. A further evolutionary step seems to be required to achieve a true sleep-regulating hormone that is no longer influenced by circadian mechanisms, body temperature regulation, and the circulating nutrient level. On the basis of this observation, it is suggested that this substance may regulate the hibernation of invertebrates. In the early stages of the purification and screening procedures for sleep-promoting substance.