SGK1 was cloned as glucocorticoid regulated gene and in turn regulates renal channels and transporters. The present study explored the contribution of SGK1 to glucocorticoid effects on electrolyte metabolism and blood pressure (BP). To this end SGK1 knockout mice (sgk1-/- ) and their wild type littermates (sgk1+/+) were treated for 14 days with dexamethasone (DEX, 3 mg/kg, b.w., i.p.) with or without additional saline load. Prior to treatment fluid intake, urinary flow rate, urinary Na+ , K+ or Cl- excretion, plasma electrolyte and glucose concentrations as well as BP were similar in sgk1 -/- and sgk1+/+mice. DEX did not significantly alter renal Na+ , K+ and Cl- excretion, tended to decrease renal Ca2+ excretion in sgk1 +/+mice, significantly increased renal Ca2+ excretion in sgk1 -/- mice and significantly decreased renal phosphate excretion in sgk1 +/+mice. DEX significantly increased fasting blood glucose and plasma leptin concentrations in both genotypes. DEX increased BP in sgk1+/+ mice, an effect significantly blunted in sgk1-/- mice. Subsequent replacement of tap drinking water with saline increased fluid intake, urinary flow rate, and urinary NaCl excretion in both genotypes, but increased plasma K+ in sgk1 -/- mice, only. Saline loading increased BP in both, sgk1-/- and sgk1+/+mice and dissipated differences between genotypes. The observations reveal SGK1-dependent and -independent glucocorticoid effects on electrolyte metabolism and BP.