The influence of enteric nerves on intestinal ion and sugar transport was investigated in 3- to 4-wk-old suckling mice. Whole thickness segments of jejunum were mounted as flat sheets in flux chambers equipped to electrically stimulate nerves in the intestinal wall. Tetrodotoxin significantly reduced basal short-circuit current in a subset of tissues containing 3-O-methylglucose in the mucosal bath. Electrical field stimulation of intrinsic nerves evoked an increase in short-circuit current of 86 +/- 15 microA/cm2 that was due to an increase in active chloride secretion with no significant change in the net movement of other ions. The secretory response to neural stimulation was abolished by tetrodotoxin and reduced by the muscarinic antagonist, atropine. Mucosal-to-serosal fluxes of 3-O-methylglucose were not altered by the cholinergic agonist carbachol. These results show that ion transport in the suckling mouse jejunum is regulated by the enteric nervous system. Neural stimulation evokes a chloride secretory response that is mediated by acetylcholine and other noncholinergic transmitters. Sugar transport in the murine small intestine does not appear to be influenced by muscarinic cholinergic agonists.