The gut neuropeptide, neuromedin U octapeptide (NMU-8) produced transient elevations in short-circuit current (EC50 = 0.7 nmol/l) after its contraluminal administration to sheets of porcine distal jejunal mucosa in vitro. Mucosal responses to NMU-8 were unaffected by 1 mumol/l atropine or hexamethonium, but were abolished by tetrodotoxin (0.1 mumol/l), dependent upon extracellular Cl, and underwent tachyphylaxis upon repeated peptide application. NMU-8 did not affect contractility of isolated jejunal longitudinal muscle. Thus, NMU-8 appears to selectively modify intestinal ion transport through interactions with non-cholinergic enteric neurons.