Intro. The renal distal convoluted tubule (DCT) participates in the regulation of renal sodium (Na) excretion and blood pressure. DCT epithelial cells exhibit structural plasticity, a classic example being the hypertrophy observed in rodents treated with loop diuretics, which is associated with increased rates of Na transport in the DCT (1). However the relationship between epithelial structure and function in hypertensive, salt-retaining states has not been characterised (notwithstanding indirect evidence of increased Na transport in the hypertrophic DCT seen in mouse models of Gordon’s syndrome (2,3)). DCT hypertrophy has been observed in mice lacking 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) (4) and we hypothesised that in this context it would be associated with increased Na transport in the DCT, contributing to the hypertensive phenotype. Methods. Male 11β-HSD2 knockout mice and wild-type controls were sacrificed at one of two ages (60 or 120-150 days). Right kidneys were formalin-fixed and the DCTs labelled by immunohistochemistry using an antibody to the NaCl co-transporter, NCC. Left kidneys were homogenised to prepare protein used in Western blots probed with anti-NCC. Urinary Na excretion was determined in separate cohorts. Mice were anaesthetised with thiobutabarbital (167mg/kg I.P.) and catheters inserted into the jugular vein, carotid artery (for blood pressure recording and blood sampling) and bladder. They were given a continuous I.V. infusion of saline containing 0.25% FITC-inulin. After 60 mins equilibration, fractional Na excretion (FENa, urinary Na excretion expressed as a fraction of filtered Na) was determined during serial 40 min sampling periods taken at baseline, following the epithelial Na channel blocker benzamil (BZM, 2mg/kg I.V. bolus then 1mg/kg/hr infusion) and following BZM plus the NCC inhibitor hydrochlorothiazide (HCTZ, 2mg/kg bolus). The incremental response to HCTZ, ΔFENa provided an index of Na transport in the DCT. Values are mean ± SEM compared by unpaired t-test. Results. Knockout mice exhibited hypertrophy and hyperplasia in the DCT at both ages (figA) and had more abundant NCC protein (figB; n=8, p<0.05). Despite this, ΔFENa was not statistically different from wild-type mice (figC; knockout vs WT at 60 days: 5.06±0.78 vs 5.93±1.45; at 120-150 days: 5.73±1.36 vs 6.55±0.66; n=6-8 each group). Conclusion. There is dissociation of structure from Na transport function in the DCT of 11β-HSD2 knockout mice. This surprising finding contradicts the prevailing hypothesis that structural changes in the renal tubular epithelium are associated with changes in transport function (1) and has implications not only for the regulation of renal Na excretion but also our general understanding of the relationship between structure and function in transporting epithelia.