The present invention is directed to methods for identification of compounds that affect wakefulness, attention deficit hyperactivity disorder, chronic fatigue syndrome and mood disorders (e.g., depression) through interaction with the hypocretin receptor system. The present invention is also directed to detection of abnormal levels of hypocretin in a subject, as well as detection of an abnormal immune response against hypocretin (orexins) and/or their receptors, where detection of abnormal hypocretin levels or detection of an abnormal immune response is indicative of a sleep disorder, particularly of narcolepsy. The present invention is also directed to a methods relating to the detection of a mutation or polymorphism in the gene encoding the hypocretin receptors, the detection of antibodies disrupting the function of gene encoding hypocretin receptors and hypocretin polypeptides, and the use of hypocretin biological markers in predicting treatment response using compounds interacting with the hypocretin receptor system.