A clearance study of Cd was carried out in rats that had received an intravenous bolus of CdCl2 or Cd-saturated metallothionein-II (Cd-MT-II) at 0.3 mg Cd/kg body weight. Urinary concentrations of Cd, and those corrected by the urine-plasma inulin ratio, were higher, by 2 or 3 orders of magnitude, for Cd-MT-II than for CdCl2. Fractional clearance of Cd was 0.0006 to 0.0029 for CdCl2, and 0.130 to 0.487 for Cd-MT-II. These findings denoted that the glomerular filtration of Cd was greater in the Cd-MT-II administration than in CdCl2 administration. This difference in the glomerular filtration of Cd gave a clear explanation for the greater nephrotoxic potential of Cd-MT-II. Also, our data revealed that when Cd was administered as Cd-MT-II, the concentration of Cd was 20 to 70 times higher at the end-point of the renal tubules than at its starting-point. This and the histopathological reports so far strongly suggest that the distally located tubules are highly resistant to intraluminal Cd.