Effect of cadmium (Cd) intoxication on renal acid-base regulation was studied in adult male Sprague-Dawley rats. Cd intoxication was induced by subcutaneous injections of CdCl2 at a dose of 2 mg Cd/kg/day for 3∼4 weeks. In Cd-intoxicated animals, arterial pH, PCO2 and plasma bicarbonate concentration decreased, showing a metabolic acidosis. Urine pH and urinary bicarbonate excretion increased and titratable acid excretion decreased with no change in ammonium excretion. In renal cortical brush-border membrane vesicles derived from Cd-exposed animals, the Na⁢/H⁢ antiporter activity was significantly attenuated. These results indicate that chronic exposures to Cd impair the proximal tubular mechanism for H⁢ secretion (i.e., Na⁢/H⁢ antiport), leading to a metabolic acidosis.