Atrial natriuretic factor (ANF) is a 28 amino acid polypeptide hormone secreted mainly by the heart atria in response to atrial stretch. ANF acts on the kidney to increase sodium excretion and GFR, to antagonize renal vasoconstriction, and to inhibit renin secretion. In the cardiovascular system, ANF antagonizes vasoconstriction, and shifts fluid from the intravascular to the interstitial compartment. In the adrenal gland, ANF is a powerful inhibitor of aldosterone synthesis. ANF participates importantly in the natriuretic response to acute and chronic volume overload. ANF's property of shifting fluid from the vascular to the interstitial compartment acts as a buffering device, guarding against excessive plasma volume expansion in face of an increased total extracellular fluid volume. ANF is also a physiological modulator of GFR, and mediates nephron hyperfiltration and natriuresis when salt excretion is threatened by a reduction in the number of nephrons. Guanylyl cyclase (GCA) receptors mediate the effects of ANF by generating cGMP. Clearance receptors remove ANF from the circulation by receptor-mediated endocytosis, and serve as a hormone buffer system to impede large inappropriate fluctuations in plasma levels of ANF. The specific structure-function-dynamics relationships of these receptors serve to modulate the role of ANF in pressure-volume homeostasis.