The comparative renal toxicity of rats after injection of cadmium (Cd) and zinc (Zn)-metallothioneins (MTs) with different Cd Zn ratios at the same dose of 200 μg MT-bound Cd kg was studied. From determination of the urinary excretion of protein, aspartate aminotransferase (AST) and glucose, which are indices of Cd-induced renal damage, the extent of the renal toxicity of the MTs used here was in the order ( 1Cd 0Zn )-MT = ( 2Cd 1Zn )-MT > ( 1Cd 2Zn )-MT > ( 1Cd 6Zn )-MT. The characterization of Cd, Zn and Cu in the urine after injection of MTs was examined using a Sephadex G-75 column. ( 1Cd 0Zn )-MT injection showed that Cd was present mainly in lower-molecular-weight fractions, with only small amounts of Cd in the MT fraction. Upon injection of other MTs, Cd was present mainly in the MT fraction and increased with decreasing Cd Zn ratio. Zn was present mainly in lower-molecular-weight fractions and Cu mainly in the MT fraction, indicating the replacement of MT-bound Zn by Cu. The cumulative urinary excretion of Cd during 12 days after injection of MTs decreased with increasing Cd Zn ratio. The Cd content of the kidney and liver increased with increasing Cd Zn ratio. The results of this study indicate that in rats injected with MTs with different Cd Zn ratios, the renal uptake of Cd increases with increasing Cd Zn ratio, resulting in more severe renal damage.