The mechanisms by which cadmium (Cd) stimulates the synthesis of hepatic and renal metallothionein were investigated in rats. In the liver the incorporation of 35S and 14C labels from cystine showed a lag period of about 2 h and maximum incorporation into metallothionein took place 8--12 h after injection of 30 mumol CdCl2/kg. The incorporation of the labels into renal metallothionein was faster than into the hepatic protein; the lag period was less than 1 h and maximum incorporation occurred 4--5 h after the Cd injection. Cycloheximide inhibited the amino acid incorporation into both hepatic and renal metallothionein. Actinomycin D treatment, however, inhibited hepatic metallothionein synthesis only. These results suggested that at the dose level employed Cd regulated the biosynthesis of metallothionein in the liver at the transcriptional level and in the kidney at the translational level.