1. Healthy volunteers and patients with a major depressive disorders were administered 1.5 mg RS 86 (a cholinergic agonist) and placebo in a randomized double-blind cross-over design at 10 p.m. prior to bedtime. 2. Polysomnographic recordings demonstrated a significantly more pronounced shortening of REM latency after cholinergic stimulation in depressed patients compared to healthy subjects. 3. Even those depressed patients displaying placebo REM latencies in the normal range showed sleep onset REM periods after cholinergic stimulation. 4. The results support the reciprocal interaction model of NonREM-REM sleep regulation and the cholinergic-aminergic imbalance model of depression.