Study of thyroid function tests in (i) untreated hypothyroidism, (ii) hypothyroidism during treatment with triiodothyronine (T3), and in (iii) the normal newborn fetus has provided, in each case, data which support the view that thyroxine (T4) has intrinsic hormonal activity other than that due to in vivo conversion to T3. Of 41 clinically hypo thyroid patients with elevated serum TSH and subnormal serum free T4, 8 (19%) had normal serum free T3 concentration. Thus, normal serum free T3 in absence of normal serum free T4 is not a sufficient condition to sustain euthyroidism. In four hypothyroid patients given 75 μg T3 per day, serum concentrations of total and free T3 were supranormal during most of the day. Together with previously published information indicating that 75 μg of T3 is no more than necessary to maintain euthyroidism and to suppress elevated serum TSH to normal, our data suggest that maintenance of euthyroidism may require a supranormal concentration of serum T3 because serum T4 is subnormal in this situation. Tested under identical conditions, serum total and free T3 concentrations in the newborn term fetus were significantly lower than those in normal adult subjects; these values were more comparable to those seen in adult hypothyroid patients. However, the mean serum TSH in hypothyroid patients was about 20 fold higher than that in the term fetal cord sera. These data suggest that the lower mean serum TSH in the newborn may be the result of free T4 which was present in cord sera in a concentration comparable to that seen in normal adult subjects and much greater than that in hypothyroid adults.