Single-injection renal clearance methods based on plasma clearance alone, without urine collection, are sometimes met with skepticism. They require data extrapolation to infinite time, which is hard to justify a priori. It has been asserted that they are less accurate for rapidly cleared tubular agents than for slowly cleared glomerular filtration rate agents. In this study, we compare urine-based and urine-free methods for the tubular agents 99mTc-MAG3 and 131I-OIH. Methods: In 18 patients, dual-tracer plasma data were obtained from 4 to 90 min after injection (nine samples). Urine was also collected for 90 min (in two voidings). The urine counts were corrected for residual bladder activity by pre- and postvoid dual-channel gamma camera images. Results: When comparing the two methods of clearance calculations, the difference between urine-based and urine-free measurements was 1 ± 5 ml/min for 99mTc-MAG3 and 23 ± 8 for 131I-OIH (mean ± s.e. of the mean). For 99mTc-MAG3, the regression line did not differ significantly from the line of identity. The correlation coefficient was 0.94 for both agents. Conclusion: Urine collection is not necessary to measure renal clearance, even for the rapidly cleared tubular agents, except at low clearance levels (when the small absolute error corresponds to a large percentage error).