The administration of the synthetic estrogen, ethinyl estradiol, in an oral dosage of 0.5 mg. daily to normal male and female subjects produced a prompt elevation in the levels of plasma phenylhydrazine-reacting (Porter-Silber) chromogens and corticosterone. More than 80 per cent of the plasma phcnylhydrazine-reacting chromogens could be accounted for as cortisol. The urinary corticoids were decreased to 30 to 50 per cent of the control levels after two to three weeks of estrogen administration. The urinary 17-ketosteroids and aldosterone showed little or no change. Cortisol and corticosterone when infused in 100 to 200-mg. quantities disappeared from the plasma at a decreased rate after administration of estrogen. Cortisone and the dihydro and tetrahydro metabolites of cortisol disappeared at a normal rate. Estrogen therapy was associated with a decrease in the rate of synthesis of cortisol and corticosterone. These markedly elevated levels of plasma cortisol after treatment with estrogen were not associated with the usual signs and symptoms of hypercortisolemia and this was interpreted in terms of an increase in the fraction of protein-bound cortisol, which is thought to be biologically inactive.