Basic and clinical research on sleep and its pathologies form the heart of a proposed research program. The major components of the program are as follows: *Research on the etiologies of human and canine narcolepsy This program will utilize in vivo and in vitro investigation methods in both canines and humans to answer genetic and neurochemical questions about narcolepsy with the long range goal of the development of new clinical therapeutic strategies. This program is housed in an environment which has a large population of narcoleptic patients in a computerized clinical database, and a well established colony of dogs affected with a genetically transmitted form of narcolepsy. *Research on the circadian control of sleep and wakefulness This program seeks to understand the role of circadian timing systems in manifestations of sleep and wakefulness. Utilizing a sophisticated automatic scoring system with the capacity to record 128 animals simultaneously, we are studying long term circadian sleep/wake manifestations as they relate to a host of manipulations including activity feedback to the clock, several neurochemical studies, and the interaction of sleep loss and circadian timing. *Research on the homeostatic aspects of human sleep and sleepiness/alertness This research is based on the theoretical construct that the circadian regulation of sleep and the homeostatic regulation of sleep are two independent and isolated processes. The research will test homeostatic regulation in two groups of patients with normal circadian timing. One group is the "alert" insomniac who experiences optimal daytime alertness even when experiencing the effects of reduced and disturbed sleep at night. The other group is the patient with narcolepsy where, in the face of profound sleepiness, there is no evidence of appropriate associated changes in sleep parameters. It is hypothesized in both groups that deprivation and satiation procedures will yield results which are the opposite of normal. In the upcoming award period, there will also be the further development of a comprehensive multidisciplinary basic sleep research program.