Glucocorticoids stimulate gastric acid secretion, an effect favouring the development of peptic ulcers. Putative mechanisms linking stimulation of the glucocorticoid receptor to acid secretion include the serum- and glucocorticoid-inducible kinase 1 (SGK1) which is known to regulate a variety of transporters and channels including KCNQ1, a channel involved in gastric H+ secretion. The present study explored the contribution of SGK1 to the effects of glucocorticoids on gastric acid secretion in mice. According to Real-time PCR gastric SGK1 transcript levels were enhanced by a 4 day treatment with 10 mg/g BW/day dexamethasone (dex). H+ secretion in parietal cells from gastric glands was estimated from Na+ independent realkalinization (DpH/min) following an ammonium pulse, as determined by BCECF fluorescence. During control conditions DpH/min was similar in sgk1-/- (0.028±0.009) than in sgk1+/+ (0.030±0.011). Dex increased DpH/min significantly (p<0.05) more in sgk1+/+ (0.125±0.02) than in sgk1-/- mice (0.076±0.01). Omeprazole (50mM) decreased DpH/min to 0.009±0.003 in dex treated sgk1+/+ and to 0.007±0.002 in dex treated sgk1-/-. In conclusion, stimulation of H+ secretion by glucocorticoids does require participation of SGK1.