The loss of the neurotransmitter hypocretin (also called orexin) is responsible for human narcolepsy. It has been speculated that this hypothalamic peptide is the master coordinator of arousal. However, our recent work in mice and rats reveals a much more selective role. We find that Hcrt knockout (KO) mice are unable to remain awake and equally impaired when their task is to work for food or water reward during the light (normal sleep) phase. However, they are unimpaired relative to wild type (WT) when working for reward during the dark phase or when working to avoid shock in the light or dark phases. In WT, activity of Hcrt neurons, as indicated by the expression of Fos in Hcrt neurons, occurs only in the light phase when working for positive reinforcement. Fos is not expressed when unearned rewards are presented, when working to avoid negative reinforcement, or when given unavoidable shock, conditions that elicit maximal EEG arousal. Fos is not expressed in the light phase when light is removed. These findings may indicate the substrate for a prior report that narcoleptics do not show the arousal response to light seen in normals or patients with hypersomnia or depression. This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction.