The cholinergic-adrenergic balance hypothesis of affective disorders postulates noradrenergic overactivity and cholinergic hypoactivity in mania and the converse in depression. Some evidence for cholinergic contributions to mood regulation derives from the antimanic and depressiogenic activity of physostigmine and arecoline. However, both drugs have pharmacodynamic and pharmacokinetic disadvantages. Therefore, the orally active muscarinic agonist RS 86 was tested in a double-blind dose-response study for its psychotropic effects in one healthy volunteer. A dose-dependent anergic-anhedonic syndrome was identified in comparison to placebo. The study confirms the physostigmine syndrome to be mediated by muscarinic, possibly Ml receptors, and gives further support to the hypothesis of a cholinergic modulation of mood and behavior in man.