The perceived importance of C-type natriuretic peptide (CNP) in the mammalian vasculature has been raised by its recent identification as an endothelium-derived hyperpolarizing factor (EDHF). This aspect of its biological activity is likely to be significant in the regulation of vascular tone, local blood flow and systemic blood pressure. However, the importance of CNP to cardiovascular homeostasis is likely to extend beyond that of a ‘hyperpolarizing factor'; indeed, there is evidence that CNP has a key role in preventing smooth muscle proliferation, leukocyte recruitment and platelet reactivity. As such, endothelium-derived CNP is likely to exert a strong anti-atherogenic influence on blood vessel walls and represent a new therapeutic target in the fight against inflammatory cardiovascular disorders. Moreover, this profile of activity defines a new paradigm for the biological significance of EDHF.