Captopril facilitates detection of unilateral renovascular hypertension by selectively reducing glomerular filtration rate in affected kidneys. To determine if volume depletion augments this response, we compared the effects of captopril, furosemide, and combined furosemide plus captopril on individual kidney computer-derived clearances of99mTc-diethylenetriamine pentaacetic acid (DTPA) and [l31I] o-iodohippurate in two-kidney, one clip Goldblatt hypertensive rats and normal controls. In clipped kidneys, captopril reduced DTPA clearance significantly from baseline (from 0.31 ± 0.02 to 0.19 ± 0.04 ml/min/100 g;p< 0.02) whereas furosemide alone had no effect (0.28 ± 0.03 ml/min/100 g). Combined furosemide plus captopril further reduced clipped kidney DTPA clearance to a level significantly less than captopril alone (0.10 ± 0.02 ml/min/100 g;p< 0.02). Clipped kidney o-iodohippurate clearance was not changed from baseline by any treatment. In contralateral undipped and normal kidneys, DTPA clearance did not decline from baseline following either captopril or furosemide plus captopril treatment. Since the dose of captopril used (3 mg/kg by intraperitoneal injection) did not reduce systolic blood pressure of hypertensive rats significantly, these changes probably reflect intrarenal rather than systemic hemodynamic effects of converting enzyme inhibition and are consistent with the hypothesis that captopril interferes with glomerular nitration in stenotic kidneys by reducing efferent arteriolar vascular resistance. Prior volume depletion accentuates the effect of captopril on stenotic kidney glomerular filtration rate, providing improved functional discrimination of stenotic kidneys from contralateral undipped and normal kidneys. These results indicate that furosemide-induced volume depletion may increase the diagnostic sensitivity of captopril-enhanced WmTc-DTPA renography in the detection of unilateral renovascular hypertension.