Chronic treatment of rats with choline caused a decrease in the hypothermic response to pilocarpine. The action of choline on the muscarinic receptors is consistent with electrophysiological and binding studies, supporting a direct muscarinic action for choline. Administration of direct muscarinic agonists has been shown to cause a decrease in the number of muscarinic receptors. Thus, the long-term use of cholinergic precursors could have some adverse effects on central cholinergic functioning.