In healthy pregnant women, the regulation of thyroid function depends upon several factors. Three factors act independently to increase thyroid hormone requirements: 1) the marked increase in the binding capacity of serum due to high TBG levels; 2) the direct stimulation of the thyroid by human chorionic gonadotropin, acting as a thyrotropic hormone; and 3) the increase in placental deiodinating activity, which may contribute to modify thyroid hormone metabolism. These stimulatory events result in a physiological adaptation of the maternal thyroid gland to pregnancy, as long as the availability of iodine for the thyroidal "machinery" remains sufficient. Our studies were performed in an area where the iodine intake is precisely at the lower limit of the needs for healthy non pregnant adult subjects (less than 100 micrograms/day). In these conditions, decreased iodine availability during gestation leads to relative iodine deficiency and hence, pregnancy constitutes a "challenge" for the thyroid gland. It was shown that excessive thyroidal stimulation occurred in as much as one third of pregnancies in Brussels, accompanied by relative hypothyroxinemia, marked elevation in serum TG levels and goitrogenesis. About 10% of women had developed a goiter at parturition, which was only partially reversible during the postpartum period. A randomized prospective trial was then undertaken in euthyroid pregnant women who were below 16 weeks of gestation at initial presentation and who fulfilled biochemical criteria of excessive thyroidal stimulation (high molar T3/T4 ratio, low normal free T4 index, elevated serum TG). Thyroid function and volume were monitored sequentially during gestation.(ABSTRACT TRUNCATED AT 250 WORDS)