Neuropharmacological data suggest involvement of the biogenic amines in narcolepsy. In humans, for example, drugs that increase biogenic amine concentrations in the synaptic cleft ameliorate symptoms of narcolepsy. Thus, agents that block monoamine reuptake (e.g., tricyclic antidepressants), potentiate monoamine release (e.g., methylphenidate), or inhibit monoamine oxidase possess therapeutic efficacy (1,2). Pharmacological experiments with genetic and nongenetic forms of the canine disease confirm these findings (3-5). In previous work, we compared monoamine metabolite concentrations in cisternal cerebrospinal fluid (CSF) collected from normal dogs and from adult miniature French poodles with a nongenetic but severe form of narcolepsy. Steady-state concentrations of dopamine and serotonin metabolites were lower in the CSF of the affected animals, and data collected with the use of the acid transport inhibitor probenecid suggested reduced turnover of serotonin and norepinephrine (6). These results suggested an abnormality in monoamine metabolism in the narcoleptic animals, and led us to undertake regional neurochemical studies in narcoleptic and normal animals.