To test the hypothesis that depression and REM sleep share common cholinergic mechanisms the authors administered arecoline 25 min after completion of the first REM period to 14 patients with remitted bipolar affective disorder, 15 normal controls, and 5 subjects with a personal or family history of affective disorder. The second REM period occurred significantly sooner in the remitted patients than in the normal controls. The patients also had a significantly higher density of eye movements during the first REM period and a higher percentage of REM sleep. The authors believe that increased cholinergic sensitivity and REM density may be biological markers of increased vulnerability to bipolar affective illness.