We have determined that differences in expression of aldosterone synthase (AS) affect responses to a low-salt diet. In AS-null mice (AS^−/−), but not in wild-type, low salt significantly decreased plasma sodium and increased potassium. The increased urine volume (1.5×wild-type) and decreased urine osmolality (0.7×wild-type), present in AS^−/− mice on normal salt, became more severe (2.3×wild-type and 0.5×wild-type) on low salt, but neither changed in wild-type. In both genotypes, plasma vasopressin was similar on normal and low salt, and desmopressin injection significantly increased urine osmolality. Renal mRNA levels for aquaporin 1 and 3 were unchanged by genotype or diet and epithelial sodium channel and Na⁺-K⁺-2Cl⁻-cotransporter by genotype. In AS^−/− mice, aquaporin 2 mRNA increased on normal salt, whereas Na⁺Cl⁻-cotransporter and cortex K⁺ channel mRNAs decreased on both diets. The low blood pressure of AS^−/− mice was decreased further by low salt, despite additional increases in renin, intrarenal arterial wall thickness, and macula densa cyclogenase-2 mRNA. In AS^+/− mice on normal salt, adrenal AS mRNA was slightly decreased (0.7×wild-type), but blood pressure was normal. On low salt, their blood pressure was less than wild-type (101±2 mm Hg versus 106±2 mm Hg), even though renin mRNA increased to 2×wild-type. We conclude that aldosterone is critical for urine concentration and maintenance of blood pressure and even a mild reduction of AS expression makes blood pressure sensitive to low salt, suggesting that genetic differences of AS levels in humans may influence how blood pressure responds to dietary salt.