The radioimmunological determinations of immunoreactive ‘angiotensin IF do not truly reflect angiotensin-(l-8)octapeptide levels, and thus cannot provide an accurate reflection of the efficacy of angiotensin-converting enzyme (ACE) inhibition. Elaborate methods are necessary to measure specifically the octapeptide angiotensin II. This methodology confirms that ACE inhibitors reduce circulating angiotensin II and that tolerance to the angiotensin II-lowering effect of ACE inhibitors does not develop, even after prolonged administration. Furthermore, a marked reduction of angiotensin II levels can be shown even in patients with primary aldosteronism. At peak blockade of ACE, the level of plasma angiotensin II is still related to circulating active renin and angiotensin I. The possible independent role of tissue renin-angiotensin systems in determining vasomotor tone is an interesting hypothesis. However, any discussion of whether tissue or plasma renin determines the pharmacologic effect of ACE inhibitors should be based on the simultaneous measurement of angiotensin-(l-8)octapeptide under steady-state conditions in tissue and plasma.