Recently identified hypothalamic peptides called orexins (or hypocretins) have been implicated in the sleep-wake cycle and in sleep disorder narcolepsy. Neuropathological studies have shown that in patients with narcolepsy, global reduction in the expression of orexins occurs due to the loss of orexin neurons in the hypothalamus. Cerebrospinal fluid analysis has confirmed a reduced or undetectable level of orexin-A in most narcolepsy patients. In this study, measurement of plasma orexin showed significantly lower concentrations in patients with narcolepsy than in age- and gender-matched normal controls. These data suggest that low levels of orexin-A in plasma could serve as a biological marker for narcolepsy.