To examine the physiological role of atrial natriuretic factor (ANF) in the maintenance of sodium homeostasis under various conditions, we performed experiments in rats across a wide range of sodium intake, in rats with chronic renal insufficiency at extremes of sodium intake, and in rats given desoxycorticosterone acetate. After three weeks of a very low sodium diet, regular diet, or regular diet plus 1% saline as drinking water, no difference in plasma values of immunoreactive atrial natriuretic factor (IR-ANF) were identified, while rats at the lowest level of sodium intake had elevated atrial values. Normal rats, and rats with 5/6 nephrectomy has plasma values of IR-ANF which were no different irrespective of their sodium intake, nor were atrial values in these rats different. Although mineralocorticoid "escape" could be documented by changes in urine sodium excretion, neither plasma nor atrial IR-ANF values showed differences either at 24 or 72 hr after "escape". The data are consistent with previous observations that ANF serves the purpose of affecting rapid adjustments to large alterations in circulating fluid volume. Chronic high sodium intake, adaptation to renal insufficiency, and adjustment to the effect of mineralocorticoid do not appear to be associated with increased circulating plasma concentrations of IR-ANF.