Clinical and experimental work indicates that cholinergic functions might play a role in modulating affectivity in man. In this acute double-blind study either the cholinolytic agent biperiden or placebo infusions were administered to six depressed females. The Janke and Debus self-rating questionnaire (EWL-K), the modified Hamilton depression scale (HAM-D), and the Montgomery and Asberg depression scale (MADRS) were used for documentation of psychopathological change. There was an acute antidepressant effect during infusion of the active drug in comparison to placebo as measured on the global MADRS and EWL-K, but not on the modified HAM-D. Single items such as depressed mood, work and interests (HAM-D), sadness, concentration difficulties, inability to feel (MADR-S), and depressiveness (EWL-K) responded selectively and significantly to the biperiden infusion. It is concluded that cholinergic activity might be involved in the regulation of affectivity in man.