Narcolepsy is a chronic sleep disorder, and dysfunction in hypocretinergic neurotransmission has been shown to underlie the pathophysiology of this disorder. Recently, two neuromyelitis optica patients with hypersomnia, hypothalamic lesions, serum anti-aquaporin-4 (AQP4) antibodies, and reduced cerebrospinal fluid hypocretin levels were reported. We hypothesized that anti-AQP4 antibodies induce hypocretin dysfunction leading to hypersomonia in a subgroup of narcolepsy or hypersomnia patients. In this study, we screened for anti-AQP4 antibodies in sera from 251 patients with narcolepsy, 34 with other hypersomnias, and 200 healthy controls by using the radioligand binding assay method. A positive result for anti-AQP4 antibodies was found only in one healthy control subject. All the hypersomnia patients were negative for this antibody. Our results indicated that anti-AQP4 antibody is not useful as a diagnostic marker for narcolepsy and other hypersomnias.