Endothelium-derived hyperpolarising factor (EDHF) is an important regulator of vascular tone; however, its identity is still unclear. Several different molecules have been suggested, the most recent of which is the 22-amino acid peptide C-type natriuretic peptide (CNP). CNP induces hyperpolarisation and relaxation of rat mesenteric resistance artery vascular smooth muscle through activation of natriuretic peptide receptor subtype C (NPR-C) and the same potassium channels as EDHF. In addition, this peptide is released from endothelial cells of the perfused rat mesenteric bed in response to endothelium-dependent vasodilators. Thus, CNP is likely to play a vital role in regulation of vascular tone. In addition, since there is evidence that up-regulation of EDHF occurs where normal endothelium function has been compromised, modulation of this pathway represents a novel target for therapeutics in the treatment of inflammatory cardiovascular pathologies characterised by endothelial dysfunction.