Lipocalin-type prostaglandin D synthase (L-PGDS) is a brain enzyme, which produces prostaglandin D(2), a substance with endogenous somnogenic effects. Using a standardized protocol for immunonephelometric determination of cerebrospinal fluid (CSF) L-PGDS levels, we show that CSF L-PGDS levels are significantly lower in 34 patients with excessive daytime sleepiness when compared with levels in 22 healthy controls. Thus, L-PGDS may represent the first neurochemical measure of excessive daytime sleepiness.