OBJECTIVE It is now believed that diabetes sensitizes the myocardium so that superimposed hypertension with its attendant vascular changes results in progressive myocyte damage leading ultimately to congestive heart failure. In this regard, remarkable progress has been made within the past few years with a family of closely related peptides, the atrial natriuretic peptides (ANPs), which are involved in the regulation of plasma volume. Any changes in their levels and/or action can be seen to participate in the development of diabetes-induced congestive heart failure. While the literature reasonably supports the evidence for a defect in the ANP-receptor coupling system in hypertensive and diabetic animals, it is not as clear that this is the cause for heart failure. The present article attempts to demonstrate evidence for causality. METHODS The present article summarizes existing knowledge on the involvement of ANP in the induction of fluid imbalance. In particular, the role of ANP in congestive heart failure, hypertension, diabetes and congestive heart failure in diabetes is examined. Recent data in experimental hypertensive-diabetic rats, obtained from this laboratory have also been described here. RESULTS There are now several reports which indicate high plasma ANP concentrations in both patients and animals with heart failure, thus implicating a role for this peptide. The present paper deals with ANP-induced molecular changes in kidney basolateral membranes in congestive heart failure due to chronic diabetes. CONCLUSIONS Congestive heart failure in diabetes with hypertension may be due to uncoupling of the ANP-receptor effector system in the kidney basolateral membrane. It is possible that other neurohumoral agents through a wide variety of activities may also contribute to the pathophysiology of this disease.