A B S T R A C T The possibility that the autonomic nervous system may influence the function of intestinal mucosa was investigated by assessing the effect of acetyl choline on ion transport in human intestine. Isolated pieces of stripped ileal mucosa were mounted in Perspex flux-chambers and bathed in isotonic glucose Ringer's solution. Acetyl choline caused a rise in mean potential difference (8.8-12.3 mV, P < 0.002) and short circuit current (287.7-417.2 A'A -cm-2, P < 0.01) (n = 12), observable at a concentration of 0.01 mM and maximal at 0.1 mM. This effect was enhanced by neostigmine and blocked by atropine. Isotopic flux determinations revealed a change from a small mean net Cl absorption (+ 0.58) to a net Cl secretion (-4.3 Aeq-cmf'-h P < 0.001) due predominantly to an increase in the serosal to mucosal unidirectional flux of Cl (10.63-14.35 ueq. cm . h-' P < 0.05) and a smaller reduction in the mucosal to serosal flux (11.22 to 10.02 /Aeq cm-' h' P < 0.05). Unidirectional and net Na transport was unaffected. A similar electrical and ion transport response was observed in a single study of two pieces of jejunal mucosa. In the absence of glucose net chloride secretion was produced and again an insignificant effect on net sodium transport was noted. Acetyl choline did not provoke a sustained effect on mucosal cyclic adenine nucleotide levels although a short-lived cyclic adenine nucleotide response was seen in some tissues 20-30 s after drug addition.These studies demonstrate that acetyl choline does influence human intestinal ion transport by stimulating chloride secretion and suggest a possible mechanism by A preliminary report of this work was presented at the British Society of Gastroenterology, Southampton, April 1975 and at the European Society for Clinical Investigation, Rotterdam, April, 1975. Received for publication 20 August 1975 and in revised formn 13 May 1976. which the parasympathetic nervous system could be concerned in the control of ion transport. INTRODUCTION It has long been thought that the autonomic nervous system may influence intestinal absorption and secretion. Sympathetic denervation in the dog and the cat caused an intestinal secretion which was blocked by atropine(1) and the spontaneous secretion of Thirty-Vella loops of dog ileum was similarly prevented by atropine (2).More recently Caren and co-workers (3) showed that the secretion provoked by tactile stimulation in such isolated loops was inhibited by atropine and hexamethonium. Pilocarpine (4) and eserine (5) caused intestinal secretion and bethanechol, a cholinergic agent, was shown to induce a net secretion of chloride in dog jejunum (6). In view of these suggestive pieces of evidence the present investigations were undertaken to examine in more detail the influence of acetyl choline on human intestinal ion transport. The results indicate that acetyl choline does influence ion transport in vitro and suggest a possible mechanism by which the parasympathetic nervous system could be involved in the control of intestina...