The renin-angiotensin system is one of the humoral mechanisms involved in the regulation of blood pressure. Even though the preliminary investigations can be traced as far back as 1898, it was only with the pioneering efforts of the research groups of Page in the United States and Braun Menendez in Argentina that we began to understand the molecular basis of this blood pressure regulating mechanism. Renin is a proteolytic enzyme, produced mainly in the juxtaglomerular apparatus of the kidney, which acts on the circulating α-globulin angiotensinogen, produced by the liver (Figure 1). The result of this enzymatic action is the formation of the decapeptide angiotensin I, which has very little, if any, biological activity. Removal of the C-terminal dipeptide histidylleucine from this decapeptide by the angiotensin-converting enzyme present in lungs and other organs yields the octapeptide angiotensin II. This peptide is a very potent vasoconstrictor agent and also the main physiological stimulus for the release of aldosterone from the adrenal gland. This mineralocorticoid, in turn, induces sodium and water retention, leading, therefore, to an increase in blood pressure by a "volume" mechanism. The relevance of the renin-angiotensin system in blood pressure regulation under normal or pathological circumstances has been very controversial. Studies with animal models and clinical observations with patients of varied etiology indicate a clear involvement of the renin-angiotensin system in hypertension of renovascular origin. However, the role of this system in human hypertension of unknown origin (essential hypertension) and in those animal models that are assumed to be a correlate of essential hypertension, i.e., the spontaneous or genetic hypertensive rat, is still the subject of considerable debate. An alternate approach to the study of the role of the renin-angiotensin system than that of measuring blood levels of intermediates is the use of specific blockers, and a detailed evaluation of this approach and its implications for the treatment of human hypertension is the subject of this article.