OBJECTIVE To investigate whether plasma angiotensin II (Ang II) determines the effects of the renin-angiotensin system or whether tissue uptake of renin and localized production of Ang II might account for any cardiovascular, renal, hormonal or drinking effect of circulating renin. METHODS Intravenous infusions of renin (0.6 ng/min; n = 10) and Ang II (3.5 ng/min; n = 10) that produce similar plasma Ang II levels were compared for 2 weeks with vehicle (n = 7) in conscious rats after a 1-week control period. Mean arterial pressure (MAP) and the heart rate were measured continuously. Hormones and renal function were measured twice weekly. Plasma Ang II and recovery data were measured in seven additional rats. RESULTS In renin- and Ang II-infused rats, respectively, plasma Ang II increased similarly from 4.5 +/- 0.8 and 4.4 +/- 0.9 to 10.8 +/- 0.7 and 10.6 +/- 0.7 pg/ml and declined similarly in the second week to 7.0 +/- 1.1 and 7.0 +/- 1.5 pg/ml. Plasma renin increased from 4.2 +/- 0.7 to 21.7 +/- 1.3 and fell from 5.9 +/- 0.5 to 0.6 +/- 0.2 ng/ml per h respectively. Plasma prorenin fell similarly (> 70%); angiotensinogen was unchanged. MAP rose initially by 25.6 +/- 1.2 and 23.3 +/- 0.9 mmHg and by an additional 21.1 +/- 2.4 and 27.4 +/- 1.8 mmHg on days 5-8. The heart rate fell gradually but transiently by -11% in both. Although the initial MAP rise was slower in renin-infused rats (P< 0.05) MAP returned to baseline within 2 h after both infusions were stopped. Changes in renal vascular resistance, renal blood flow, glomerular filtration rate, urinary sodium, potassium and water excretion and water intake were not significantly different between renin- and Ang II-infused rats. CONCLUSIONS Intravenous infusions of low doses of renin or Ang II into conscious rats increase MAP identically. MAP increases in two phases 5-8 days apart, in coordination with transient falls in the heart rate. Renin- and Ang II-induced chronic hypertension are identically sustained by very small increases in plasma Ang II. Blood pressure increases more slowly with renin infusions, consistent with tissue binding. Notwithstanding, no evidence was obtained for a physiological role of tissue-bound renin in causing the cardiovascular, renal, hormonal and drinking responses measured in this study.