In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 ± 5 to 4 ± 2 ml/min, p < 0.05), ERPF (from Ill ± 13 to 21 ± 10 ml/min, p < 0.05) and UV (from 0.86 ± 0.15 to 0.075 ± 0.045 ml/min, p < 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 ± 18 to 237 ± 27 ml/min, p < 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes. These results suggest that the dramatic decreases in thalamate and hippurate excretion of the poststenotic kidney after acute ACE-inhibition are not due to a similarly dramatic fall in GFR or ERPF but mainly to tubular retention of the