It has become established that heart has an endocrine function because it synthesizes and secretes a family of peptide hormones, called Atrial Natriuretic Peptide (ANP), with potent diuretic, natriuretic, vascular smooth muscle-relaxing activity and complex interactions with the hormonal and nervous systems. Because ANP has important volume-regulatory characteristics, it is postulated to play a central role in volume homoeostasis under normal conditions and in several pathophysiological states, such as congestive heart failure. ANP is able to counterbalance all the detrimental effects of activation of the neuro-hormonal system in patients with heart failure may lead to new therapeutical protocols that can prevent the progression from compensation to overt heart failure. An integrated approach for the assessment of the endocrine function of the heart is proposed, consisting of four different, but complementary, steps: 1) evaluation of gene expression of ANP in the myocardial cell; 2) determination of circulating and tissue levels of ANP; 3) in-vivo assessment of the main turnover parameters of the hormone; 4) studies on localization and identification of ANP receptors. These procedures have been employed in physiological, pharmacological and/or clinical studies. The development and the standardization of new methods for the assessment of endocrine function of the heart will not only increase our understanding of the physiological regulation of production, secretion, and function, and of the pathophysiological role of ANP and its related peptides, but also may pave the way for further progress concerning our knowledge of more general physiological and pathophysiological mechanisms of the cardiovascular system itself.