Although the perifornical lateral hypothalamic area (PeFLH), which contains orexin/hypocretin (OX) neurons, plays an important role in arousal-related behaviors, its neuromodulatory inputs are incompletely understood. The present study examined the role of glutamatergic inputs to the PeFLH in various arousal-related behaviors. Adult male rats received a microinjection of the ionotropic glutamate receptor agonists AMPA (1 and 2 mM) or NMDA (1 and 10 mM), or vehicle into the PeFLH, and were placed in an open field; 90 min later, rats were perfused for immunohistochemistry for OX and c-Fos as a marker of neuronal activation. AMPA injections dose-dependently increased locomotion, rearing, and drinking. NMDA injections (at 10 mM) increased locomotion and feeding. All these behaviors (except feeding) were positively correlated with the number of c-Fos/OX-immunoreactive neurons. These results support the role of ionotropic glutamate receptors on OX (and other) neurons in the PeFLH in the regulation of locomotor and ingestive behaviors.