Loss of hypocretin cells or mutation of its receptors causes narcolepsy. In canine genetic narcolepsy, produced by a mutation of the Hcrtr2 gene, symptoms develop postnatally with symptom onset at 4 weeks of age and maximal symptom severity by 10-32 weeks of age. Canine narcolepsy can be readily quantified. The large size of the dog cerebrospinal fluid (CSF) cisterns allows the withdrawal of sufficient volumes of CSF for accurate assay of hypocretin levels, as early as postnatal day 4. We have taken advantage of these features to determine the relation of CSF hypocretin level to symptom onset and compare hypocretin levels in narcoleptic and normal dogs. We find that by 4 days after birth, Hcrtr2 mutants have significantly higher levels of Hcrt than normal age and breed matched dogs. These levels were also significantly higher than those in adult narcoleptic and normal dogs. A reduction followed by an increase in Hcrt level coincides with symptom onset and increase in the narcoleptics. The Hcrtr2 mutation alters the normal developmental course of hypocretin levels.