Escape from the sodium-retaining effects of aldosterone (ALDO) is thought to occur as a result of natriuretic compensatory mechanisms triggered by extracellular fluid volume expansion. The purpose of the present study was to determine whether increases in plasma levels of atrial natriuretic peptide occur during ALDO escape in conscious dogs (n = 6) maintained on a fixed sodium intake (60 meq/day). Infusion of ALDO at a rate of 15 micrograms X kg-1 X day-1 for 6 days decreased sodium excretion (UNaV) from 59.1 +/- 4.0 to 36.2 +/- 5.7 meq/day on day 1, and then UNaV gradually returned to control levels by day 5 of ALDO infusion. Net cumulative sodium balance progressively increased during ALDO infusion, reaching a peak value of 88.8 +/- 21.3 meq/day on day 5. Mean arterial pressure increased from 85 +/- 3 to 95 +/- 4 mmHg, and plasma renin activity decreased from 1.32 +/- 0.27 to 0.32 +/- 0.07 ng angiotensin (ANG) I X ml-1 X h-1 during ALDO infusion. Plasma levels of atrial natriuretic peptide averaged 67.5 +/- 8.9 pg/ml during control and increased to a peak value of 120 +/- 18 pg/ml by day 4 of ALDO infusion. Three to four days after ALDO infusion was stopped, plasma levels of atrial natriuretic peptide averaged 46 +/- 5 and 50 +/- 6 pg/ml, respectively. In summary, escape from the sodium-retaining effects of ALDO is associated with significant increases in the circulatory levels of atrial natriuretic peptide.