As is the case for most small molecules in the body, the thyroid hormones are involved in interaction with proteins. The present discussion has centered on the hormone-protein interactions which occur in plasma. Although some of this is with proteins which also engage in other binding reactions, at least one protein, TBG, seems to exist only for the purpose of binding the thyroid hormones, and the interaction energy is extremely high. While this would lead us to suspect that is has an important role in hormone physiology, its function seems to be only of secondary significance. The peculiar role of PA in the transport of a vitamin as well as thyroid hormones also suggests a specific function, but none has become apparent. Knowledge of these proteins and their variation are of considerable importance to several commonly employed diagnostic tests of thyroid function. Their greatest importance at the present time, however, seems to be as models of thyroid hormone-protein interaction. The rapid advances being made in the isolation and characterization of TBG and PA provide the means to gain detailed chemical knowledge about two rather different types of binding sites. Hopefully, this will form the basis for similar knowledge about the active sites for the hormones on cellular proteins. Conceivably, this will help to further our understanding about the mechanism of hormone action.