Introduction: Crohn´s disease is often accompanied by watery diarrhea, the pathophysiology of which is incompletely understood. Aim: We investigated the expression and function of NHE3, the major intestinal Na+ absorptive transport mechanism, in the terminal ileum and proximal colon of IL-10 deficent mice. Methods: NHE3 mRNA expression in the ileal and proximal colonic tissue of IL-10 deficient mice in the early stage of inflammation and healthy wt mice were studied by quantitative PCR, NHE3 protein localization by immunohistochemistry, sodium absorption in Ussing-chambers, and NHE3 transport rates fluorometrically in NHE3-expressing surface cells. Results: IL-10 deficient mice developed mild diarrhea and a virtual loss of active Na+ absorption in inflamed tissue. NHE3 mRNA was strongly upregulated, and the surface cell area which stained apically for NHE3 were found to penetrate more into the openings of the hypertrophied crypts. NHE3 activity was strongly decreased and displayed impaired regulation. Conclusion: The data suggest that in the early stage of immune-mediated intestinal in-flammation, mRNA expression of the Na+/H+ exchanger NHE3 is strongly upregulated and NHE3 protein is correctly located in the brush border membrane, but nevertheless transport activity is severely impaired due to as yet unknown intracellular events.