Up to one billion people live in areas where they may be at risk from I deficiency. Many of the debilitating effects of the deficiency may be irreversible, consequently it is essential to understand the mechanisms whereby lack of I can cause disease through decreased thyroxine and 3, 3',5-triiodothyronine (T3) synthesis. Since Se has an essential role in thyroid hormone metabolism, it has the potential to play a major part in the outcome of I deficiency. These effects of Se derive from two aspects of its biological function. First, three Se-containing deiodinases regulate the synthesis and degradation of the biologically active thyroid hormone, T3. Second, selenoperoxidases and possibly thioredoxin reductase (EC 220.127.116.11) protect the thyroid gland from H2O2 produced during the synthesis of thyroid hormones. The mechanisms whereby Se deficiency exacerbates the hypothyroidism due to I deficiency have been elucidated in animals. In contrast to these adverse effects, concurrent Se deficiency may also cause changes in deiodinase activities which can protect the brain from low T3 concentrations in I deficiency. Animals with Se and I deficiency have changes in serum thyroid hormone concentrations that are similar to those observed in patients with I deficiency disease. However such animal models show no thyroid involution, a feature which is characteristic of myxoedematous cretinism in man. These observations imply that if Se deficiency is involved in the outcome of I deficiency in human populations it is likely that other interacting factors such as goitrogens are also implicated. Nevertheless the protection of the thyroid gland from H2O2 and the regulation of tissue T3 levels are the functions of Se that are most likely to underlie the interactions of Se and I.