The regional differences in secretory and absorptive responses to cholera toxin (CT) and to infection by enterotoxigenic Escherichia coli (ETEC), producing heat-stable enterotoxins, were studied in the porcine small intestine. Proximal, mid and distal small intestine from newly weaned piglets were used. Na+ and Cl- fluxes and electrical parameters in CT-stimulated and ETEC-infected intestine were measured by the Ussing chamber technique. In addition, CT-induced fluid accumulation in ligated loops was measured. CT induced fluid accumulation, which was highest in the proximal segment and decreased in the aboral direction of the small intestine. In addition, CT induced a net Cl- secretion in the proximal and mid segments, while net Na+ absorption was reduced only in the proximal segment. The ETEC-infected intestine showed a net increase in Cl- secretion in the proximal part and abolished the net Na+ absorption in the distal segment. These results demonstrate segmental differences in the epithelial transport responses to enterotoxin from Vibrio cholerae and to ETEC infection. This needs to be taken into consideration in relation to oral rehydration studies.