Effects of an inhibitor of the uptake of noradrenaline (maprotiline, 75 and 150 mg) and two inhibitors of the uptake of 5-hydroxytryptamine (zimelidine, 100 and 200 mg; indalpine, 25 and 50 mg) on sleep were studied in healthy man. Maprotiline reduced the duration of rapid eye movement (REM) sleep and increased the duration of stage 2 sleep, and there was evidence of sedation the next day. Zimelidine and indalpine reduced the duration of REM sleep, but also reduced the total sleep time and increased wakefulness and stage 1 (drowsy) sleep. It is suggested that in acute studies, the effects of inhibition of uptake on sleep are likely to arise from presynaptic inhibition of release of transmitter, although other mechanisms cannot be excluded. Suppression of REM sleep is believed to be due to the balance between cholinergic and monoaminergic influences being disturbed rather than a specific effect arising from the modulation of a particular transmitter.