Animal studies have indicated that technetium-99m L,L-ethylenedicysteine (99mTc-L,L-EC) may be a promising tracer agent for renal function studies. We have performed a paired study with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and 99mTc-L,L-EC in six male volunteers. In both cases, iodine-131-labelled o-iodohippurate was co-injected as an internal biological standard. The analog images between 0 and 30 min p.i. were of identical diagnostic value for both tracer agents. The two renograms were similar in all volunteers. The mean 1-h plasma clearance for 99mTc-MAG3 and 99mTc-L,L-EC was significantly different, respectively 382.9 +/- 17.1 ml/min per 1.73 m2 versus 460.2 +/- 47.7 ml/min per 1.73 m2 (P < 0.003). The urinary excretion after 30 min p.i. was 69.4% +/- 5.6% of the injected dose for 99mTc-MAG3 versus 66.5% +/- 2.5% for 99mTc-L,L-EC (P > 0.05) and after 60 min p.i. respectively 83.1% +/- 3.9% versus 79.8% +/- 4.3% (P > 0.05). 99mTc-L,L-EC has a very low plasma protein binding (31% +/- 6.8%) as compared to 99mTc-MAG3 (88% +/- 5.2%) and a larger volume of distribution. Although the exact mechanism responsible for the high plasma clearance of 99mTc-L,L-EC is not yet fully known, we conclude that this new agent merits further clinical evaluation in patients to establish its value as a renal radiopharmaceutical.