The effect of angiotensin converting enzyme (ACE) inhibition on the sensitivity of radionuclide renography in the diagnosis of a unilateral renal artery stenosis was tested both in a conscious dog model and in the human situation. ACE inhibition (10 mg enalaprilic acid, intravenously) markedly improved the sensitivity of [123I]hippuran renography in 10 renovascular hypertensive dogs with a mild to moderate unilateral renal artery stenosis from 50 to 100%. This improved sensitivity was due to an ACE-inhibition-induced delayed tracer handling at the stenotic side without an appreciable change in the renographic curve at the contralateral side. A similar phenomenon was observed in 15 hypertensive patients with an angiographically proved unilateral renal artery stenosis. Both [123I]hippuran and 99mTc-diethylenetriaminepentaacetic acid (DTPA) handling was delayed on the stenotic side after oral enalapril treatment. However, only a moderate increase in sensitivity was observed comparing control renograms to ACE-inhibition renograms: from 87 to 93% for hippuran, and from 60 to 86% for DTPA. Eight of these 15 patients underwent either surgery or angioplasty resulting in a successful correction of the stenosis. Hypertension was more or less cured in five patients. Each of these patients had shown an ACE-inhibition-induced change in the renogram at the stenotic side, suggesting that such a response may predict the curability of the hypertension. However, of the three patients that showed no blood pressure change upon successful revascularization, two showed a positive ACE-inhibition renogram. In conclusion, in an ideal setting as obtained in animal experiments, ACE inhibition improves the sensitivity of renographic studies to 100%. However, its value in the clinical setting needs more standardization.