Although the enteric nervous system (ENS) has been shown to regulate mucosal secretion under physiological conditions, its potential contribution in pathophysiological situations is unknown. To address this question, we used a pig model of secretory diarrhea which is induced after oral treatment with the porcine specific enteropathogenic Escherichia coli Abbotstown (EcA). Two days after enterotoxigenic challenge the distal jejunum was isolated and mucosa/submucosa preparations including plexus submucosus were mounted in Ussing chambers. The net electrogenic transport of electrolytes was measured as short-circuit current (Isc) and responses to electrical field stimulation (EFS) serve as a measure of neurogenic secretion. In diarrhea baseline Isc was 52% less negative which could be explained by a higher net Cl- secretion due to the infection. EFS- evoked neurogenic secretion was decreased by almost 90% in EcA animals indicating down-regulation of secretory ENS pathways. Maximal stimulation of Cl- secretion by forskolin and carbachol were nearly identical in both groups indicating similar maximal secretory capacities. Again EFS responses were significantly lower in EcA animals after forskolin (cAMP pathway) and carbachol (Ca2+ pathway) pre-stimulation. The results suggest that delivering of pro-secretory neurotransmitters by the ENS may be down-regulated in situations when secretory processes are markedly stressed, i.e. in acute secretory diarrhea.