The conventional protein kinase C isoenzyme β (PKC-β) is expressed in various structures of mouse kidney. To get insights into the function, PKC-β knockout (–/–) and wild-type (+/+) mice were studied. Under basal conditions, PKC-β–/– mice exhibited a higher systolic blood pressure (in awake mice), normal plasma concentrations of Na<sup>+</sup> and K<sup>+</sup>, and normal plasma pH. Urine osmolality and 24-hour excretion of fluid, Na<sup>+</sup>, K<sup>+</sup> and albumin were not different between genotypes, but urine pH was more alkaline in PKC-β–/– mice. Inulin clearance experiments under anesthesia confirmed a higher systolic blood pressure and revealed normal glomerular filtration rate and fractional excretion of fluid, Na<sup>+</sup> and K<sup>+</sup> in PKC-β–/– mice. The ability to restrict renal Na<sup>+</sup> excretion in response to a low Na<sup>+</sup> diet was unaltered in PKC-β–/– mice. Chronic acid loading (NH<sub>4</sub>Cl) did not affect blood pH in PKC-β+/+ mice, but induced a modest metabolic acidosis in PKC-β–/– mice. In conclusion, first evidence is presented that (i) PKC-β contributes to the regulation of arterial blood pressure, and (ii) PKC-β is required for normal acid-base balance, which may relate to its expression and function in intercalated cells of the collecting duct.