Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical 99m Tc(CO) 3 -nitrilotriacetic acid, 99m Tc(CO) 3 (NTA), were essentially identical to those of 131 I ortho-iodohippuran ( 131 I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. Methods: 99m Tc(CO) 3 (NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of 99m Tc(CO) 3 (NTA) were coinjected with 9.25 MBq (250 mCi) of 131 I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. Results: There was no difference in the plasma clearances of 99m Tc(CO) 3 (NTA) and 131 I-OIH, 475 6 105 mL/min versus 472 6 108 mL/min, respectively. The plasma protein binding and red cell uptake of 99m Tc(CO) 3 (NTA) were 43% 6 5% and 9% 6 6%, respectively; both values were significantly lower (P , 0.001) than the plasma protein binding (75% 6 3%) and red cell uptake (17% 6 5%) of 131 I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% 6 4% for 99m Tc(CO) 3 (NTA) and 91% 6 6% for 131 I-OIH (P 5 0.96). Image quality with 99m Tc(CO) 3 (NTA) was excellent, and the renogram parameters were similar to those of 131 I-OIH. Conclusion: Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of 99m Tc(CO) 3 (NTA) is comparable to that of 131 I-OIH.Key Words: 99m Tc-tricarbonyl; renal radiopharmaceuticals; 99m Tc(CO) 3 (NTA); 131 I-ortho-iodohippuran ( 131 I-OIH); 99m Tc-mercaptoacetyltriglycine ( 99m