Plasma clearances of inulin (Cin),99mTc-DTPA (CDTPA), and urographic contrast media (CCM) were determined simultaneously in 31 patients with varying levels of renal function evaluated in the setting of affiliated cardiac and renal transplantation programs. Cinand CDTPAwere calculated from the ratio of simultaneously measured plasma concentration and urine excretion rate of these test agents (U×V/P). CCMwas derived from x-ray fluorescence measurement of plasma iodine (PI) content following intravenous injection of 50 ml of nonionic, low-osmolar contrast media (180 mg I/ml). Urine collections were not required for CCMdeterminations. No adverse reactions attributable to CM occurred in any patient, and follow-up serum-creatinine values did not differ significantly from prestudy levels.CCMdetermined from the rate of decline in PI between 3 hr and 4 hr following administration of contrast media (“slope-intercept” technique) [CCM—SI] correlated closely with corresponding levels of Cin(r =.86,P< 0.0001), and CDTPA(r = 0.89,P< 0.0001). Mean CCm-SI/Cinand CCM-SI/CDTPAratios for the entire study cohort were 1.09 ± 0.06 and 1.08 ± 0.06, respectively. CCM-SI determinations also correlated well with CCMlevels derived from a single measurement of PI (“single sample” technique) made at 3 hr following injection of contrast media (r = 0.94,P< 0.0001). Both CCM-SI and CCMdetermined by the “single sample” method (CCM-3°SS) tended to overestimate Cinand CDTPA, however, when the latter were <20 ml/min/1.73 m2(mean CCM-SI/Cinand Ccm-3°SS/Cinratios 1.36±0.14 and 1.95+1.0, respectively.Reproducibility was evaluated by paired comparison of 3-hr vs. 4-hr “single sample” CCMdeterminations (r = 0.99,P< 0.0001). In addition, analysis of the variation in iodine content between duplicate specimens obtained at each of these time intervals revealed a mean ratio of 1.0±0.01 (P= NS vs. identity).Contrast clearance determination utilizing the slope-intercept method is accurate, safe, pragmatic, and more precise than serum-creatinine and endogenous-creatinine clearance for measurement of renal function in clinical transplantation.