Cadmium is an environmental pollutant which has been shown to be toxic to a number of tissues in mammalian systems. These studies will make clear what dose is necessary to produce injury to the various tissues, which tissue is most sensitive to cadmium, and if there is a marked difference in the toxic sign between animals that receive one high, single dose and those that receive multiple, low doses over a long time. Information will be gained on the importance of metallothionein on the toxicity of cadmium. Does metallothionein alter the distribution of cadmium? Do metallothionein and cadmium levels in the tissues continue to rise with prolonged administration at different doses, or is a plateau achieved? What is the mechanism by which cadmium is excreted into the bile? Can it be enhanced by treatment with microsomal enzyme inducers? Will interruption of the enterohepatic circulation increase the elimination of cadmium from the body? If we can answer these very basic questions, then we should be able to treat cadmium poisoning on a more informed basis.