A model for narcolepsy is developed on the basis of data obtained from brains collected at post mortem from three patients with narcolepsy. The concentration of dopamine, noradrenaline, and serotonin and their metabolites was measured in many brain regions. The number and affiniiy of the 3-H-spiperone and 3-Hprazocin binding sites was also measured in many of these regions to characterize the O-2 dopamine and alpha-l-noradrenergic receptors, respectively.Evidence for significantly increased serotonin levels and serotonin turnover was found in many brain regions. Noradrenaline turnover was increased in the frontal cortex. DOPAC/DA was significantly reduced in the striatum. The number of D-2 dopamine receptors, however, was markedly increased in this region. The number of alpha-1-noradrenergic receptors was significantly decreased in the frontal cortex and amygdala.Our ncurochemical data demonstrating increased NA and 5-HT turnover suggest that locus cocrulcus noradrenergic neurones and raphe serotonergic neurones are ovcractivc in narcolepsy. Current evidence posits that increased activity in these neurones depresses the activity of cholinergic pcdunculopontinc (PP) RF.M sleep effector neurones. PP neurones project to and stimulate the dopamincrgic substantia nigra compacta neurones. Decreased PP activity in narcolepsy, thus, could lead to pontine cholinergic supersensitivity and could also reduce the firing rales of dopaminergic neurones, as the low slriatal ratio of DOPAC/DA suggests. An increase in the number of D-2 dopamine receptors in the striatum may result. The reason for the increased activity of the noradrenergic and serotonergic neurones remains to be determined, but immune inactivation of alpha-l-noradrenergic receptors may be the initiating event.Low alpha-1 -noradrencrgic receptor numbers may account for the chronic drowsiness of narcolepsy. The repealed entry into sleep, and into RHM sleep in particular, may represent a homeostalic response to increase these receptor numbers and, thus, to increase alertness. Some therapeutic implications of this model arc presented in the discussion. KKSUMK Un modclc dc la narcolepsic cst developpc a partir de donnees obtenucs sur des cerveaux post-mortem appanenant a trois patients souffrant de narcolepsie. Ix;s concentrations en dopamine, noradrenaline, serotonine et leurs metabolites ont ete mesurees dans plusieurs regions cerebralcs. On a mesure aussi lc nombre el raffiniie des sites d'attache de la 3H Spiperone et de la 3H frazocin dans plusieurs de ces regions en vue de caractcriscr les rcccptcurs dopamine D2 et noradrenergiques alpha-1.Dans dc nombrcuscs regions cerebralcs les nivcaux de serotonine et le changemenl scrotoninergique ctaient augmentcs significalivemenl. l.