Numerous studies have shown that administration of atrial natriuretic factor (ANF) increases urinary sodium excretion and urine flow, decreases blood pressure, and inhibits renin and aldosterone release. However, the role of endogenous ANF in the regulation of renal sodium excretion, blood pressure, plasma renin activity, and aldosterone level remains to be elucidated. To examine this issue, endogenous ANF was blocked by administering rat ANF-(99-126) specific antiserum (Ab) to anesthetized rats (n=7). Control animals received either no injection (time controls, n=10) or preimmune serum (n=8). Blockade of endogenous ANF caused a 28±0.09%, 47±0.08%, and 51±0.08% fall in sodium excretion at 15, 30, and 45 minutes after Ab injection (p<0.05, p<0.01,p<0.01, respectively). Urine flow fell 35±7% at 45 minutes after ANF inhibition (p<0.05). Plasma ANF levels were suppressed to undetectable levels. However, there were no changes in blood pressure throughout the experiment nor plasma renin concentration when measured at 45 minutes after Ab injection. Interestingly, plasma aldosterone concentration increased significantly (by approximately 50%, p<0.025), in response to Ab. Completeness of blockade was demonstrated by the absence of sodium excretion response to exogenous ANF (500 ng). In either the time control or the preimmune serum group, urinary excretion, blood pressure, plasma ANF, plasma renin concentration, and plasma aldosterone concentration were unchanged throughout the experiment. In contrast to the Ab group, a challenge with exogenous ANF (500 ng) increased sodium excretion by 2.17 μeq/min in the preimmune serum group. These data suggest that endogenous ANF contributes to the regulation of urinary sodium excretion and plasma aldosterone concentration in the anesthetized rat. However, endogenous ANF does not appear to contribute to the regulation of blood pressure or plasma renin concentration.