The distal convoluted tubule (DCT) plays key roles in blood pressure (BP) homeostasis. Reabsorbing up to 7% of the sodium load, DCT length changes with demand, optimizing sodium delivery into the collecting duct. The Na-Cl co-transporter (NCC) is the predominant route for apical sodium entry. Aldosterone activates NCC but the conventional paradigm of mineralocorticoid protection by 11β-hydroxysteroid dehydrogenase 2 does not apply: the enzyme is not expressed in the DCT and NCC can be regulated by glucocorticoids. Glucocorticoid receptor (GR) heterozygous mice on a standard (0.25%) sodium diet have elevated BP and increased circulating corticosterone. We found in vivo that NCC reabsorbs ~2% of the filtered sodium load in both wild-type and GR+/- mice. When mice were a fed high salt diet (2.5%), a reduction of thiazide-sensitive transport was seen in wild type mice but not in GR+/-. Heterozygotes entered positive sodium balance (P<0.01, n=6, one way ANOVA) and BP increased (P<0.05 n=16, one way ANOVA). High sodium diet caused a moderate increase (P<0.05) in mRNA abundance for slc12a3, the gene encoding NCC, in GR+/-, but not in controls (n=8, Student’s t-test). Surprisingly, the high sodium diet increased total expression of NCC in both genotypes and there was no difference in expression between genotypes under either dietary regimen (P>0.05, n=6, Student’s t-test). These data indicate that inappropriate NCC activity contributes to salt sensitive hypertension in GR haploinsufficiency. Sustained NCC activity in vivo does not correlate with protein abundance and may reflect alterations in post-translational modification (e.g. phosphorylation), protein-protein interactions or membrane trafficking.