The toxicological significance of the placental metallothionein (MT) was studied from the viewpoint of cadmium (Cd) intoxication. The Cd concentration was higher in the placenta than the kidneys until 8 hr after a single injection of 109CdCl2, but was very low after administration of 109Cd-MT. Compared with lower doses, fetal Cd began to increase at the dose of 2 mg/kg. Alkaline phosphatase activity in the placenta was significantly decreased, and dead fetuses appeared at this dose. The MT concentration was not increased by the Cd injection but the ratio of Cd/Zn in MT increased proportionally to the dose up to 2 mg/kg. MT was detected in the placenta during all stages of pregnancy, and its concentration was higher in the earlier stage. The metal bound to MT was mainly Zn, and very little Cu was bound. In the mice that became pregnant after 109Cd accumulation, redistribution of 109Cd was not observed. MT-I and -II in the placenta were identified by column chromatography and immunoblotting methods. These findings suggest that the placental MT might play a protective role against Cd toxicity by trapping of the metal.