We explored the effects of 12-hour infusion of atrial natriuretic peptide (α-rANP: rat, 1–28) on arterial acid-base balance, using 5 6 nephrectomized rats with chronic renal failure. Before the infusion, nephrectomized rats had a higher mean arterial blood pressure, greater urine volume, and lower creatinine clearance than the normal controls, but they did not show a significant difference in arterial hydrogen ion concentration (pH), plasma bicarbonate concentration (HCO 3 −), partial pressure of carbon dioxide (PCO 2), plasma base excess (BE), or plasma ANP concentration. α-rANP infusion produced a continuous blood pressure reduction in both nephrectomized and control rats. Urine volume and urinary sodium and potassium excretion tended to increase at 2-hour infusion, but not at 12-hour infusion. In the controls α-rANP significantly increased pH from 7.47 to 7.50, and decreased PCO 2 by 14%. In contrast, in nephrectomized rats α-rANP significantly decreased pH from 7.48 to 7.44 HCO 3 − by 13%, and BE from −0.07 to −3.22 meq/1. Rats with chronic renal failure had greater reduction in HCO 3 − than the controls (p<0.05). There was no difference in plasma ANP level 0 between the two groups. Thus, it is indicated that the long-term infusion of α-rANP reduces pH in rats with chronic renal failure, thereby adversely affecting the acid-base balance.