Effects of purified rabbit anti-rat 25-amino acid atrial natriuretic peptide (ANP) immunoglobulin G (IgG) on renal sodium excretion and glomerular filtration rate were studied in a rat model of congestive heart failure (CHF) having high circulating ANP levels. Bolus injection of anti-ANP into anesthetized rats with surgically induced myocardial infarction (MI) significantly and markedly depressed both absolute and fractional urinary excretion of sodium without affecting mean arterial pressure or glomerular filtration rate. By contrast, anti-ANP failed to affect these renal functions in normal or acutely water-deprived rats. Nonimmune IgG did not affect renal function in MI rats. These results indicate that high circulating ANP plays an important role in sodium homeostasis of congestive heart failure: by promoting sodium excretion, ANP opposes the tendency of sodium retention characteristic of CHF.