Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R‐basal) and short circuit currents (ISC; secretion) under basal conditions (ISC‐basal) and after electrical field stimulation (ISC‐EFS) of nerves in 2221 resectates from 435 patients. ISC‐EFS was tetrodotoxin‐sensitive and of comparable magnitude in small and large intestine. ISC‐EFS or R‐basal were not influenced by patients´ age, gender or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC‐EFS depended on epithelial cAMP‐driven chloride and bicarbonate secretion, but not on amiloride‐sensitive sodium absorption. While atropine‐sensitive cholinergic components prevailed in ISC‐EFS of duodenum, jejunum and ileum, PG97‐269‐sensitive (VIP receptor1 antagonist) VIPergic together with L‐NAME‐sensitive nitrergic components dominated ISC‐EFS in colonic preparations. Differences in numbers of cholinergic or VIPergic neurons, sensitivity of epithelial muscarinic or VIP receptors or stimulus frequency dependent transmitter release were not responsible for the region specific transmitter contribution to ISC‐EFS. The low atropine‐sensitivity of ISC‐EFS in the colon was rather due to high cholinesterase activity because neostigmine revealed cholinergic components. Colonic ISC‐EFS remained unchanged after tachykinin, P2X, P2Y or A1/2 receptor blockade. R‐basal was smaller but ISC‐basal was higher in small intestine. Tetrodotoxin and bumetanide decreased ISC‐basal in all regions suggesting nerve‐dependent secretory tone. ISC‐basal was atropine‐sensitive in the small and PG97‐269‐sensitive in the large intestine. This comprehensive study revealed novel insights into region specific nerve‐mediated secretion in human small and large intestine. This article is protected by copyright. All rights reserved