Selenocysteine has been identified in the active center of types 1 and 3 iodothyronine deiodinases, two important enzymes regulating the formation and degradation of the active thyroid hormone, 3,5,3'-triiodothyronine (T3). Selenium is thus required for such complex processes as normal growth, brain development, and metamorphosis, all of which are thyroid hormone dependent. Structural and functional analyses of the type 1 deiodinase mRNA allowed identification of the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the 3' untranslated region of the mRNA. SECIS elements with conserved sequence and structural features are also present in the 3' untranslated regions of the mRNAs encoding selenoprotein P and the glutathione peroxidase family of selenoproteins. These elements are necessary and sufficient for directing selenocysteine incorporation into the deiodinases and the other mammalian selenoproteins.