To facilitate the genetic study of sleep, we documented that rest behavior
in Drosophila melanogaster is a sleep-like state. The animals choose a pref
erred location, become immobile for periods of up to 157 min at a particula
r time in the circadian day, and are relatively unresponsive to sensory sti
muli. Rest is affected by both homeostatic and circadian influences: when r
est is prevented, the flies increasingly tend to rest despite stimulation a
nd then exhibit a rest rebound. Drugs acting on a mammalian adenosine recep
tor alter rest as they do sleep, suggesting conserved neural mechanisms. Fi
nally, normal homeostatic regulation depends on the timeless but not the pe
riod central clock gene. Understanding the molecular features of Drosophila
rest should shed new light on the mechanisms and function of sleep.