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Over a period of several years, methods of measuring circulating angiotensin II have been progressively improved and it has now become possible to measure circulating angiotensin II with a high degree of accuracy. The main ingredients in this new methodology are bonded-phase silica for quantitative angiotensin extraction from biological fluids and antibodies with a high affinity to angiotensin II to provide for the sensitivity of the radio-immunoassay, high performance liquid chromatography to guarantee the specificity for the angiotensin-(1-8)octapeptide, and a renin inhibitor in the blood sampling tube to prevent any in vitro angiotensin II generation. With this new methodology it can be demonstrated that after the first administration of a full dose of an angiotensin converting enzyme (ACE) inhibitor, plasma angiotensin II virtually disappears from the circulation, whereas with chronic administration which induces a marked increase in renin secretion and thereby in angiotensin I levels, angiotensin II clearly remains present in plasma at peak inhibition, though at a much lower level than before ACE inhibition. Plasma angiotensin II levels were decreased equally and dose-dependently by the administration of two renin inhibitors, CGP38560A and A64662. However, in man these compounds have so far only been tested with single administration. In conclusion, the measurement of plasma angiotensin II equally reflects the degree of ACE and renin inhibition, and is therefore the only logical approach to evaluation of the efficacy and potency of ACE inhibitors and renin antagonists.