Sleep deprivation (SD) is an effective, however short-lived, method of treatment of depression. Preliminary findings suggest that the antidepressive effect of sleep deprivation is mediated by serotoninergic (5-HT) mechanisms. We therefore assessed serotoninergic activity before and after total SD (TSD) as well as after the following night sleep by investigating platelet LSD-binding, MAO B-activity, and 5-HT-content as well as plasma norepinephrine (NE) in 10 healthy men (age: 27.4 ± 2.8 years). Blood samples were drawn on three consecutive days at 0700, 1300 and 1900 h, respectively. After TSD, a significant increase of LSD-binding K D and B m a x as well as of MAO-B K M and plasma NE could be observed, which, however, vanished after consecutive night sleep. Our findings favour an increased serotoninergic transmission after TSD and thus support the hypothesis, that sleep deprivation exerts its antidepressant effects by pro-serotoninergic mechanisms.