WHILE preliminary studies associated oleamide with sleep regulation, we now characterize the involvement of oleamide in sleep using a number of techniques. Peripheral administration of oleamide to rats dose dependently suppressed motor activity in the open field, with an ED50 of 17 ± 1.5 mg/kg for the decrease in distance traveled. Moreover, endogenous oleamide concentrations increased 3- to 4-fold in the cerebrospinal fluid of rats sleep-deprived for 6 h or longer. Oleamide also decreased sleep latency to 44–64% of control values without altering other sleep parameters. Unlike many putative endogenous sleep-inducing agents, oleamide potently induces behavioral and electroencephalographic manifestations of sleep. Moreover, its endogenous concentrations and temporal associations are consistent with previous reports of its enhancement of serotonergic and GABAergic neurotransmission, which may be involved in sleep induction.