Receptor studies indicate that the clinical effects of antidepressant drugs are mediated, at least in part, by an action on neurotransmitter receptors. It seems likely that the direct receptor interactions, such as the anticholinergic, antihistaminic, and α blocking activities, are responsible for many of the side effects observed with these drugs, whereas the long term modifications in receptor binding, which appear to be secondary to some other neurochemical action, may be responsible for therapeutic efficacy.