Aldosterone (Aldo.) has been shown to stimulate luminal proton secretion and basolateral bicarbonate exchange activity in type A intercalated cells. Aldo. insufficiency results in hyperkalemic distal renal tubular acidosis. The effect of chronic aldo. insufficiency on the expression and function of renal acid-base transporters has not been systematically investigated. Animal models of aldo. insufficiency have been based on adrenalectomy also affecting other adrenal hormones involved in acid-base homeostasis. Here we examined a mouse model lacking aldo. synthase (AS KO) catalyzing the final step in aldo. synthesis. AS KO mice have no adrenal or extra-adrenal aldo. production whereas all other adrenal hormones are intact. Mice are mildly hyperkalemic and renin and angiotensin II levels are highly elevated. Wild type and AS KO mice were kept on a control diet, an acidotic diet (0.28 mM NH4Cl in drinking water), or were given the AT1 receptor antagonist losartan (3 days). AS KO mice had lower blood pH, lower bicarbonate and chloride level as well as mild hyperkalemia on control diet. These changes were accompanied by a higher urine output, a more alkaline urine, and increased water and food intake. In the kidney AS KO mice had higher AE1 mRNA and protein expression on control and acidotic diets. After losartan treatment, mRNA expression of pendrin was decreased in AS KO mice. Also, a4 and B1 H⁺ -ATPase subunits showed decreased mRNA expression and protein abundance (cortex) in AS KO mice after losartan treatment. Expression of SNAT3, PEPCK and NHE3 was not altered between WT and AS KO. Our results suggest that AS KO mice have hyperkalemic metabolic acidosis. Increased AE1 expression in AS KO on control and acidotic diet might be a compensatory mechanism due to higher levels of angiotensin II. Decreased expression of a4 and B1 subunits of H⁺- ATPase in AS KO mice, after AT1 receptor blockade by losartan suggests that these subunits might be regulated by aldo. and angiotensin II.