The present study investigated the impact of the cholinesterase inhibitor tetrahydroaminoacridine (THA; tacrine) on sleep in healthy subjects. According to the reciprocal interaction model. of non-rapid eye movement (NREM) and REM sleep regulation, which postulates a primary role of cholinergic neurotransmission for the initiation and maintenance of REM sleep, it was expected that THA would lead to an earlier onset of REM sleep. In 12 healthy subjects aged from 21 to 50 years two different doses (20 mg, 40 mg) were administered 1 hour prior to bed time and compared to placebo. Only the higher dose of THA significantly shortened REM latency. No other significant effects on sleep architecture were observed, although administration of 40 mg tacrine was associated with a decrease in sleep efficiency and a prolongation of sleep latency. Blood plasma levels of tacrine and its metabolite 1-hydroxytacrine-measured prior to sleep and during the first 90 min of sleep were significantly correlated with the onset of REM sleep in relation to the timing of-drug administration (only for the 20 mg dose). The reversible cholinesterase inhibitor THA exerts effects on REM latency comparable to; those observed with other cholinomimetic agents.