The effect of bile salts on intestinal motility is unclear. In the current study, isometric contractions of the guinea pig terminal ileum were examined in vitro. Dose-response curves to known agonists cholecystokinin (CCK), bethanechol, and KCl were constructed alone and in the presence of atropine (10(-6) mol/L), tetrodotoxin (10(-6) mol/L), and different bile salts, namely, taurodeoxycholate, tauroursodeoxycholate, taurocholate, glycodeoxycholate, and glycoursodeoxycholate. These bile salts, at levels as low as 5 and 50 mumol/L, significantly depressed (P less than 0.05) CCK-induced contractions throughout the dose-response curves and were concentration dependent. This depressant effect was not dependent on the bile salt species or any apparent physicochemical differences between them. The inhibitory effect was also specific for certain agonists such as CCK (the action of which was partially mediated by cholinergic nerves, being depressed by atropine and abolished by tetrodotoxin), field stimulation, and nicotine. Bile salts had no effect on either bethanechol- or KCl-induced contractions. Such bile salt inhibition of excitatory, cholinergic, enteric neurons may slow transit through the ileum, enhancing the time for absorption and conserving the bile salt pool.