The discovery that hypocretins are involved in narcolepsy, a disorder associated 
with excessive daytime sleepiness, cataplexy, and unusually rapid transitions to 
rapid eye movement sleep, opens a new field of investigation in the area of 
disorders of sleep and activation. Hypocretin-1 (hcrt-1) and hypocretin-2 
(hcrt-2) (also called orexin-A and orexin-B) are newly discovered neuropeptides 
processed from a common precursor. Hypocretin containing cells are located 
exclusively in the lateral hypothalamus, with widespread projections within the 
central nervous system. The role of the hypocretin system in other disorders 
causing excessive daytime sleepiness is more uncertain. This study reports the 
findings of a prospective study measuring cerebrospinal fluid concentrations of 
hypocretin-1 and hypocretin-2 in HLA DQB1*0602 positive narcolepsy with 
cataplexy, monosymptomatic narcolepsy, and primary hypersomnia. The results 
confirmed the previous observations, that hcrt-1 is deficient in narcolepsy and 
for the first time report very low levels of hcrt-1 in primary hypersomnia. It 
is also reported for the first time that there is a generalised defect in hcrt-2 
transmission in all three of these clinical entities compared with controls.