The peripheral metabolism of thyroxine (T4) was studied before and after the administration of oestrogens in 21 patients with Graves' disease and in 5 subjects with thyrotoxicosis factitia. In addition, 6 patients with Graves' disease while receiving oestrogen treatment were given 600 mg of diphenylhydantoin (DPH) orally daily; the study on the peripheral metabolism of T4 was similarly performed. Oestrogens induced the following changes in T4 metabolism: a decrease in the concentration of free T4 in the serum, an increase in serum total T4, slowing of the fractional turnover, and contraction of the distribution space. The extrathyroidal T4 pool remained unchanged. These changes led to a decrease in daily T4 degradation rate from 469 μg in the control period to 348 μg during oestrogen therapy (P < 0.001). Fifteen of these patients showed apparent clinical improvement. The 2 subjects with T4-thyrotoxicosis factitia had decreased T4 degradation and remission of symptomatology following oestrogen administration; on the other hand, 3 subjects with T3-thyrotoxicosis factitia had no appreciable amelioration of their symptoms. The administration of DPH to oestrogen-treated patients with Graves' disease induced a slight acceleration of the absolute T4 turnover. It is concluded that the decreased T4 degradation induced by oestrogens in spontaneous and iatrogenic hyperthyroidism was mediated by an increase in T4-binding globulin capacity in the serum.