Brown adipose tissue (BAT) iodothyronine 5'-deiodinase (5'D) activities are very high during fetal life but decrease 10-fold a few hours before birth. Accordingly, BAT 3,5,3'-triiodothyronine (T3) concentrations are also very high. The temporal patterns of changes in BAT 5'-D and fetal plasma insulin are similar (and differ from the pattern for catecholamines) but are not superimposable. A causal role for insulin in the activation of fetal BAT 5'-D is therefore not supported by the data. Maternal thyroidectomy leads to a decrease in the total and relative weight of fetal BAT and to a 30-50% increase in BAT 5'-D activities; BAT thyroid hormone concentrations are essentially unchanged. Fetal hypothyroidism was induced by giving methimazole and resulted in a marked decrease of BAT thyroxine (T4) and T3 concentrations. This treatment increased BAT 5'-D activity only on day 21 of gestation, but no effect was observed on day 20. The fetal 5'-D response to thyroid hormones infused into the methimazole-treated dams was studied at 21 days of gestation. The increase in BAT 5'-D induced by methimazole treatment was prevented by T4 infused into control dams but not by T3. In fetuses from thyroidectomized dams, the pattern of 5'-D regulation by thyroid hormones was impaired. It is suggested that the high concentrations of thyroid hormones present in fetal BAT might participate in the general maturation and development of fetal BAT.