Plasma clearance 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. Cin and CDTPA were calculated from the ratio of simultaneously measured plasma concentration and urine excretion rate of these test agents (UxV/P). CCM was 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 CCM determinations. No adverse reactions attributable to CM occurred in any patient, and follow-up serum-creatinine values did not differ significantly from prestudy levels. CCM determined 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 less than 0.0001). and CDTPA (r = 0.89, P less than 0.0001). Mean CCM-SI/Cin and CCM-SI/CDTPA ratios for the entire study cohort were 1.09 +/- 0.06 and 1.08 +/- 0.06, respectively. CCM-SI determinations also correlated well with CCM levels derived from a single measurement of PI ("single sample" technique) made at 3 hr following injection of contrast media (r = 0.94, P less than 0.0001). Both CCM-SI and CCM determined by the "single sample" method (CCM-3 degrees SS) tended to overestimate Cin and CDTPA, however, when the latter were less than 20 ml/min/1.73 m2 (mean CCM-SI/Cin and Ccm-3 degrees SS/Cin ratios 1.36 +/- 0.14 and 1.95 +/- 1.0, respectively. Reproducibility was evaluated by paired comparison of 3-hr vs. 4-hr "single sample" CCM determinations (r = 0.99, P less than 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.