See article by Ashley et al. [8] (pages 73–82) in this issue. Apelin, a peptide recently isolated from bovine stomach extracts, has been seen to act as an endogenous ligand of the orphan G-protein-coupled APJ receptor [1]. The structure of apelin preproteins was deduced from the sequences of the relevant cDNAs. The preproteins consist of 77 amino acid residues, with the apelin active sequence in the C-terminal regions [1]. Apelin mRNA expression was also found in the gastrointestinal tract, adipose tissue, brain, lung, kidney, liver, skeletal muscle, and cardiovascular system. In the cardiovascular system, it has been detected in endothelial cells of large conduit arteries, coronary vessels, and endocardium of the right atrium [2]. Apelin displays several activities on various systems. It has been seen to stimulate the proliferation of gastric cells in vitro and to increase the secretion of cholecystokinin in vivo [3]. A diuretic effect is consistent with its presence in the supraoptic nucleus of the hypothalamus, where it seems to inhibit the electrical activity of vasopressin-releasing neurons [4]. On the cardiovascular system, apelin exerts potent vasodilator and positive inotropic activities. Studies on mice revealed that apelin-induced hypotension is abolished by inhibition of nitric oxide (NO) synthase and that the angiotensin II hypertensive response is enhanced in APJ-deficient animals [5]. These results suggest not only that apelin vasodilatation is mediated by NO, but also that APJ receptors counteract the pressor effect of angiotensin II, possibly in response to a basal release of apelin from the … *Tel.: +39 11 6707785; fax: +39 11 670 7708. Email address: gianni.losano{at}unito.it