PPAR[gamma] agonists are potent hypoglycemic agents in the treatment of diabetic patients. Adverse effects of PPAR[gamma] agonists include fluid retention leading to edema formation. PPAR[gamma] agonists were shown to upregulate the serum and glucocorticoid inducible kinase SGK1, which regulates the renal epithelial Na+ channel ENaC and has thus been proposed to mediate the fluid retention induced by PPAR[gamma] agonists. The present experiments have been performed to test whether lack of SGK1 modifies the effect of the PPAR[gamma] agonist pioglitazone. Pioglitazone-containing food (0.02%, i.e. approx. 25mg/day/kg BW) was administered to gene targeted mice lacking SGK1 (sgk1-/-) and their wild type littermates (sgk1+/+). During 4 weeks of treatment body weight increased significantly (p<0.05) more in sgk1+/+ (+2.2±0.3g) than in sgk1-/- mice (+1.3±0.2g). Similarly, hematocrit decreased significantly (p<0.05) more in sgk1+/+ (-6.5±1.0 %) than in sgk1-/-mice (-3.1±0.6%). Plasma Na+ concentration increased significantly (p<0.05) in the sgk1+/+ mice (from 149±2 to 157±3 mM) but not in sgk1-/- mice (154±2 to 158±2 mM). The present study suggests the partial involvement of SGK1 in the fluid retention induced by the PPARg agonist pioglitazone.