Administration of Cd, Zn, Cu, or Hg increases the rate of transcription from the metallothionein-I gene in mouse liver and kidney. Maximal transcription rates occur 1 h after Cd administration in both tissues. Metallothionein-I mRNA levels, measured by cDNA hybridization, and metallothionein protein synthesis, measured by [35S]cysteine incorporation, increase simultaneously, reaching maximal levels about 4 h after Cd administration. Cd also induces metallothionein-I mRNA in all other tissues examined (spleen, heart, skeletal muscle, brain, and intestine) except testes. Comparison of the inductions by Cd and Hg shows that the kinetics of metallothionein-I mRNA accumulation as well as the stability of the resultant metallothioneins differ.