The serum and glucocorticoid inducible kinase SGK1 is up-regulated by mineralocorticoids and enhances ENaC activity in several expression systems. In gene targeted mice lacking SGK1 (sgk1-/-) transepithelial potential difference (Vte) and amiloride sensitive equivalent short circuit current (Iamil) in renal collecting duct is lower than in their wild type littermates (sgk1+/+). ENaC and SGK1 are similarly expressed in colon. In the present study Vte and Iamil were determined in colon from sgk1-/- and sgk1+/+ mice. Plasma aldosterone was significantly (p<0.05) higher in sgk1-/- than in sgk1+/+ mice. Both, Vte and Iamil were significantly (p<0.05) larger in untreated sgk1-/- than in untreated sgk1+/+ mice. A 4 day dexamethasone (dex) treatment (10mg/g BW) significantly (p<0.05) increased Vte and Iamil in both, sgk1-/- and sgk1+/+ mice as well as a 4 day treatment with DOCA (2mg/day) or a 4 day exposure to salt deficient diet. Vte and Iamil were significantly (p<0.05) higher in sgk1-/- than in sgk1+/+ mice under all three experimental conditions. In conclusion, lack of SGK1 does not disrupt colonic ENaC channel activity and does not abrogate its regulation by glucocorticoids and mineralocorticoids.