The effects of m-chlorophenylpiperazine (m-CPP) (0.5 mg/kg) on sleep architecture and behavior were examined in six healthy volunteers following a single oral dose of the drug in a randomized, double-blind, placebo-controlled study. m-CPP reduced total sleep time (TST) and sleep efficiency in all subjects. Slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep were decreased and stage 1 sleep was prolonged in a majority of subjects. Prominent behavioral and psychological effects were reported in five out of six subjects following m-CPP (but not following placebo) that interfered with sleep. The sleep disruption and behavioral activation following nighttime administration of m-CPP contrasts with the sedative properties of its parent compound, trazodone, suggesting that the hypnotic effect of trazodone is not related to the agonist profile of its metabolite, m-CPP.