Over the past 10 years, our understanding of the renin-angiotensin system has changed greatly, reflecting significant advances in this field. Studies in cell biology, the application of molecular biological techniques, and studies of angiotensin kinetics have provided evidence for the existence in various sites (cardiac, cerebral, renal, vascular and gonadal) of tissue-based renin-angiotensin system that function independently of the plasma renin-angiotensin system. These local systems contribute to the functional activity of their plasma counterpart through the local production of angiotensins I and II; at the same time, they are autonomous autocrine-paracrine systems with their own regulatory mechanisms. This multicentric organization of the renin-angiotensin system has physiologic and pathophysiologic implications. However, it also has important therapeutic consequences, since it follows that inhibition of the plasma renin-angiotensin system alone is probably not sufficient for therapeutic purposes.