Essentially all organisms (microbes, plants and animals) use an endogenous clock to activate various physiological and behavioral rhythms at the appropriate time of day. Our understanding of the clock is particularly important for human health and well being since basic physiological activities including sleep, endocrine and cardiovascular function and drug tolerance are rhythmically controlled. Moreover, shift workers have higher accident rates and lower cognitive and sensory performance, thereby making circadian control of sensory systems a timely subject for basic biomedical research. Extensive research has shown that the clock's timekeeping mechanism, called a circadian oscillator, is comprised of autoregulatory feedback loops in gene expression. Although there have been many advances in understanding the core mechanism and entrainment of the circadian oscillator, much less is known about how the oscillator controls physiological outputs. This is especially true in Drosophila, the animal in which the core mechanism of circadian timekeeping is best understood. We have recently demonstrated a robust circadian rhythm in the electrophysiological responses to odorants in the antennae, one of the principle olfactory tissues of Drosophila. Given that olfaction is a critical sensory modality used for food acquisition, predator avoidance, and social interactions in a host of diverse species including Drosophila, it is important to understand whether local oscillators in antennal cells mediate this rhythm, which components of the olfactory system are under circadian clock control, and how rhythms in olfaction affect behavior. These issues will be addressed in the specific aims of this proposal: 1) Identify circadian oscillator cells that mediate circadian rhythms in olfactory responses, 2) Define the molecular mechanisms controlling rhythmic olfactory responses in the Drosophila antennae, and 3) Characterize behavioral effects due to circadian olfactory responses in adult Drosophila.