Background: Glucocorticoids stimulate intestinal salt and water absorption via an increase in NHE3 abundancy in the enterocyte brushborder-membrane (BBM). In heterologous expression systems this mechanism is dependent on the presence of serum- and glucocorticoid-inducible kinase (SGK1) and the PDZ adapter- protein NHERF2 (E3KARP). Aim and methods: To test this model in native intestine, we treated NHERF2-deficient and wildtype as well as NHERF1/NHERF2/PDZK1-deficient and wildtype mice with dexamethasone (dexa) for 6 h and 4 d and investigated the NHE3 protein abundance in the BBM by Western-Blot analysis. Results: In small intestinal BBM of wildtyp and NHERF2-deficient mice we found an identical increase of NHE3 protein in the BBM after dexa treatment at both time points. This was not seen in NHERF1/NHERF2/PDZK1- deficient mice. Conclusions: These data indicate that not NHERF2 but NHERF1 or PDZK1 is involved in the glucocorticoid-stimulated NHE3 activation in the small intestine of mice.