The aim of this study was to define the use of the triple radiopharmaceutical renal study (TRRS) for renal scintigraphy as a physiological tool for renal evaluation, and to determine if the sensitivity and/or specificity of a renal study for the diagnosis of renovascular hypertension (RVH) could be improved by the combination of three radiopharmaceuticals (i.e., I-131 OIH, Tc-99m DTPA, and Tc-99m glucoheptonate). One hundred ninety-five patients with suspected RVH underwent TRRS, standard Tc-99m DTPA renal studies, and renal angiography. One hundred eighty-nine patients were hypertensive and ischemic nephropathy was suspected in six. Ninety-one, including three patients with ischemic nephropathy, had a renal artery stenosis of 70% or more (66 unilateral, 25 bilateral). Effective renal plasma flow (ERPF), glomerular filtration rate (GFR) (from plasma clearance of I-131 OIH and Tc-99m DTPA), and geometric renal masses (from Tc-99m glucoheptonate study) were compared to normal values corrected for body surface, to determine the severity of renal dysfunction. For the TRSS, RVH criteria included: 1) differential Tc-99m DTPA function minus differential Tc-99m glucoheptonate function of affected kidney ( < -5% or > 5%) and 2) functional parameters: ERPF = 1.6-2.0 ml/g/minute, GFR = 0.25-0.4 ml/g/minute, and filtration fraction (i.e., GFR/ERPF = 0.15-0.20) on the affected side.