The pathophysiological role of atrial natriuretic factor in patients with chronic heart failure is still unclear. Plasma ANF levels are elevated in this condition, particularly in patients with severe left ventricular dysfunction and during acute exacerbations. Drug therapy, including diuretics, vasodilators and inotropes which reduce cardiac filling pressures also reduce plasma ANF levels. In the clinical setting the measurement of ANF levels may provide a useful means of assessing salt and water retention in patients with heart failure. Intravenous infusion of ANF to patients with heart failure causes a diuresis and natriuresis, a fall in filling pressures and possibly suppression of the renin-angiotensin aldosterone system. High bolus dosing with the peptide may reduce systemic vascular resistance resulting in hypotension, which markedly attenuates the renal effects. A new pharmacological approach in this area is the development of neutral endopeptidase inhibitors, which prolong the half-life of endogenous ANF and potentiate its effects. The therapeutic potential of ANF in heart failure has yet to be realised.