In aldosterone target tissues, 11β hydroxysteroid dehydrogenase type 2 (11βHSD2) is co-expressed with mineralocorticoid receptors (MR) and protects the receptor from activation by glucocorticoids. Mutations in the encoding gene, HSD11B2, cause Apparent Mineralocorticoid Excess in which hypertension is thought to reflect volume expansion secondary to sodium retention. Hsd11b2(-/-) mice are indeed hypertensive but impaired natriuretic capacity is associated with significant volume contraction, suggestive of a urine-concentrating defect. Water turnover and the urine concentrating response to a 24-hour water deprivation challenge were therefore assessed in Hsd11b2(-/-) mice and controls. Hsd11b2(-/-) mice were found to have a severe and progressive polyuric/polydipsic phenotype. In younger mice (~2 months of age), polyuria was associated with a decreased mRNA abundance for aqp2 and aqp3. The expression of other genes involved in water transport (aqp4, slc14a2 and slc12a2) was not changed. The kidney was structurally normal and the concentrating response to water deprivation was intact. In olderHsd11b2(-/-) mice (>6 months), polyuria was associated with a severe atrophy of the renal medulla and down-regulation of aqp2, aqp3, aqp4, slc14a2 and slc12a2. The concentrating response to water deprivation was impaired and the natriuretic effect of the loop diuretic, bumetanide, was lost. In older Hsd11b2(-/-) mice, the V2 receptor agonist desmopressin did not restore full urine concentrating capacity. We find that Hsd11b2(-/-) mice develop nephrogenic diabetes insipidus. Gross changes to renal structure are observed but these are probably secondary to sustained polyuria, rather than of developmental origin.