Basal alkaline secretion of the denervated rat ileum was monitored by a pH-stat method. Changes of transepithelial electrical potential difference (PD) were also continuously registered. In other experiments net fluid transport was measured with a gravimetric method. The importance of the enteric nervous system for the recorded variables was investigated by giving i.v. hexamethonium, neuropeptide Y (NPY) or methionine-enkephalin or by stimulating electrically the mesenteric nerves surrounding the superior mesenteric artery. Alkaline secretion was inhibited by about 20% by mesenteric nerve stimulation or by neuropeptide Y (NPY) or met-enkephalin i.v. A somewhat greater inhibition (approximately 30%) of transepithelial electrical potential difference was elicited by the mesenteric nerve stimulation and NPY whereas met-enkephalin did not cause any transepithelial electrical potential difference change. Net fluid absorption was markedly diminished (by approximately 65-75%) by met-enkephalin but not by NPY. The cellular mechanisms underlying alkaline secretion were investigated by means of amiloride, SITS and acetazolamide. The basal alkaline secretion and transepithelial electrical potential difference were not influenced by 10(-3)M or 10(-4) SITS. In contrast 10(-3) M amiloride caused a significant increase of alkaline secretion but not of transepithelial electrical potential difference. A 35% reduction in the alkaline secretion but not transepithelial electrical potential difference was observed after acetazolamide had been given intravenously. A similar decrease was observed after giving hexamethonium. We conclude: (1) Enteric nerves are of comparatively small importance in controlling the ileal alkaline secretion recorded during basal conditions; (2) About 35% of the basal ileal alkaline secretion is carbonic anhydrase dependent. This mechanism is not influenced by nicotinic receptor blockade; (3) Under the present experimental conditions there may be an alkaline secretion which is concealed by a simultaneously operating Na+/H+ exchanger and; (4) No consistent quantitative correlation exists between alkaline secretion, transepithelial electrical potential difference and net field transport in the denervated rat ileum.