Female rats were fed a low iodine diet (LID) or the same diet supplemented with KI (IOD) and mated. Plasma TSH, T₄ and T₃ in thyroid, plasma, and tissues, and 5’-deiodinase activities (5’D) were measured in maternal, fetal, and neonatal samples. Plasma T₄ was markedly reduced in LID dams, TSH was increased, and T₃ was normal. Placental T₄ was decreased to 10%, and placental T₃ to 50%. In LID fetuses there was a complete depletion of both extrathyroidal and intrathyroidal stores of T₄ and T₃. The thyroid responded with increased synthesis and secretion of T₃ over T₄, as assessed from the T₃ to T₄ ratios. Near birth, brain T₄ and T₃ concentrations were only 6.7% and 12% of those in IOD fetuses, despite a marked increase in brain 5’D-II and a T₄-sparing decrease in liver and lung 5’DI. Brown adipose tissue 5’D-II increased 7-fold, and brown adipose tissue T₄ and T₃ concentrations were only decreased by 50%. After birth, the availability of iodine improved somewhat through maternal milk, and the thyroidal and extrathyroidal pools of T₄ and T₃ increased, although they remained much lower than those in IOD pups. Brain 5’D-II markedly increased in LID pups, and this together with an increase in plasma and brain T₄ ensured almost normal brain T₃ during the suckling period. The thyroidal secretion of T₃ over T₄ continued to be increased in LID pups during the suckling period and appeared to be related to their high circulating TSH levels. Both LID fetuses and newborns can respond to iodine deficiency as adults rats, but the fetus is more sensitive to LID because of its dependence on maternal T₄. The success of the adaptative mechanisms in protecting the brain from severe T₃ deficiency depends on the supply of iodine, the limiting factor for the synthesis of T₄. (Endocrinology129: 2663–2673, 1991)