The hypocretinergic system has been implicated in the generation and/or maintenance of wakefulness. Our results challenge this hypothesis. Utilizing cats as an animal model and immunocytochemical procedures for the simultaneous detection of hypocretin and Fos, we determined that hypocretinergic neurons are activated during wakefulness but only when somatomotor activity is present. These neurons are not activated during alert or quiet wakefulness in the absence of motor activity or during quiet sleep. We conclude that the hypocretinergic system is not responsible for the generation and/or maintenance of wakefulness, per se; on the contrary, we suggest that hypocretinergic neurons are primarily involved in motor functions irrespective of the animal's behavioral state.