Most thyroxine (T4) secreted from the thyroid is deiodinated in peripheral tissues. At least three isozymes are known in iodothyronine deiodinase which catalyzes the conversion of T4 to triiodothyronine (T3) or reverse T3. Type I 5'-deiodinase (5'D-I) exists in most tissues including the liver, kidney and thyroid. Type II 5'-deiodinase (5'D-II) which exists mainly in the brain, pituitary, brown fat and placenta plays an important role in the saturation of intracellular T3 receptor. Type III enzyme (D-III) which deiodinases the five positions of T3 is considered to modulate the T3 content by regulating its degradation. The complementary DNA (cDNA) for the rat and human 5'D-I has recently been cloned. 5'D-I contains a rare amino acid selenocysteine, which is essential for normal deiodinative function in humans as well as rats. On the other hand, 5'D-II, whose molecular weight is much heavier than that of 5'D-I, does not contain selenocysteine and its cDNA has not been sequenced. Little is known about the molecular characteristics of D-III. Further studies are needed to clarify the molecular mechanism by which deiodinase proteins are produced in various circumstances and to investigate the meticulous aspects of metabolic pathways other than deiodination.