Seven monozygotic twin pairs were found to display concordance for sensitivity to REM sleep induction by arecoline (intraclass correlation (ri) of 0.69, F = 5.35, p less than 0.02). The REM1-REM2 interval on the placebo night did not show significant concordance (ri = 0.05, F = 1.11, p = 0.44). Our previous study suggested that increased sensitivity to the muscarinic agonist arecoline, as measured by time to onset of the second REM period during sleep, may be an indicator of vulnerability to affective disorder. The present finding of twin concordance in response to arecoline suggests genetic variation in sensitivity of CNS muscarinic cholinergic receptors. Such increased sensitivity may play an etiologic role in affective disorder.