The aim of the this research proposal is to elucidate the direct role of T4 in the regulation of human TSH production, aside from that as a precursor to circulating T3. Given that the pituitary is more sensitive to circulating levels of T4 than peripheral tissues, the response of serum TSH either to increasing serum T4 without changing T3, or to lowering serum T3 levels without changing T4 will be examined. Preliminary results show that serum TSH can be reduced without an increase in serum FT3I by giving intermittent bolus doses of thyroxine. This approach will be applied to the treatment of patients who are receiving thyroxine to suppress TSH (thyroid cancer and nodules). The goal is to develop a schedule of thyroxine administration that achieves the desired degree of TSH suppression, but results in less tissue thyrotoxi sis.