Analogs of the thyroid hormones, thyroxine and 3,5,3'-triiodothyronine, are synthesized in order to define specific structural, functional and conformational requirements for hormone-like or hormone antagonist effects. Biological testing systems include the rat antigoiter assay, binding studies to thyroxine-binding globulin and prealbumin, binding to rat liver cell nuclei and to the solubilized thyroid hormone receptor protein, stimulation of amino acid uptake by the rat thymocyte, and binding to lymphocytes. Molecular orbital calculations are used to establish conformational characteristics and the predicted nature and strength of specific binding interactions. Computergraphics are used to visualize potential binding interactions with the crystalline structure of prealbumin. Quantitative structure-activity analyses are carried out by the Hansch approach, using regression analysis.