THYROXINE (T₄), measured as protein-bound iodine, was the first hormone to be quantitated in human serum. As a consequence, it was possible to demonstrate clear relationships between circulating T₄ concentrations and many of the physiological manifestations of thyroid hormone excess or deficiency. In 1952, 3,5,3′-triiodothyronine (T₃) was identified in human plasma and metabolic studies in man soon led to the realization that this hormone was 3–4 times as potent metabolically as T₄ (1–4). At that time, the question was first raised as to whether T₄ or T₃ was the “active” thyroid hormone (3). This question became even more pertinent when it was suggested first in 1955 (5) and shown conclusively in 1970 that T₄ could be converted to T₃ by peripheral human tissues (6, 7). These studies were made possible by the development of methods for quantitating T₃ in human serum, initially by competitive protein binding techniques, followed soon thereafter by specific and sensitive RIAs.