A congenitally or developmentally small right kidney in an adult spinal cord injury patient had only 12% of total uptake on radioiodine-labeled orthoiodohippurate renography but nevertheless had a normal-shaped time-activity curve. In a subsequent retrospective review of 175 consecutive radioiodine-labeled orthoiodohippurate renograms performed on adult patients over a 3-year period, 35 other patients with studies showing greater than 2:1 asymmetry in renal function were identified. Uptake, clearance, or both were abnormal in all 35 kidneys with less than 33.3% of function, with the left kidney more commonly affected (n = 24). Correlation from ultrasound, computerized tomography, intravenous pyelography, and angiography demonstrated acquired abnormalities associated with all 35 of these kidneys, including urinary obstruction (n = 20), renal artery stenosis (n = 9), and cortical scarring/infection and/or reflux (n = 15) (some patients had more than one diagnosis). While acquired renal function asymmetry almost always results in a smaller kidney with abnormal uptake or clearance characteristics, a congenitally small kidney may have overall reduced blood flow but still display a normal-shaped time-activity curve on radionuclide renography.