The initial clinical studies with radioactive iodine began at the University of California School of Medicine in 1938, when Drs. Joseph G. Hamilton and Mayo H. Soley administered I131 to patients with hyperthyroidism and to patients with carcinoma of the thyroid gland. Although they and others demonstrated that such therapy offered considerable promise in the treatment of hyperthyroidism, the experience in treating patients with thyroid carcinoma was disappointing, and these studies were held in abeyance for the next several years. During this period, numerous reports dealing with the use of radioiodine in carcinoma of the thyroid appeared in the literature. These reports showed that, while relatively few of these carcinomas took up significant quantities of administered radioiodine, some did respond to this therapy. In the fall of 1945, the problem of radioiodine therapy of carcinoma of the thyroid was again taken under consideration. When the program was first resumed, the investigation consisted essentially of the administration of a test dose of I131, followed by examination of the carcinomatous tissue for uptake of the isotope. A few attempts were made to influence the uptake by thyroidectomy or by the administration of thyroid-stimulating hormone (TSH); but, at least initially, the results were not very successful. As more patients were seen and studied, a few were found with tumors possessing an appreciable affinity for iodine. Thus interest grew, and a fairly intensive and systematic program evolved. The primary aims were: (a) to treat patients suffering from carcinoma of the thyroid, (b) to develop ways and means of influencing thyroid cancer tissue to take up administered I131, and (c) to study the possible adverse effects of the radiation in patients who received relatively large doses of radioiodine. Several different approaches to the treatment of thyroid carcinoma with radioiodine were in use in various medical centers. In certain of these, patients were treated only after the establishment of a minimum degree of radioiodine uptake by the neoplastic tissue. In these cases the evaluation was often an indirect one, based on measurement of urinary excretion of I131. In other centers patients with inoperable thyroid carcinomas were treated with equal doses of I131 administered at regular predetermined intervals, whether or not there was any demonstrable uptake by the neoplastic tissue. In fact, this regimen was used postoperatively as a means of prophylactic irradiation even when there was no known residual neoplastic tissue. The basic program at the University of California Hospital in San Francisco lay somewhere between these two approaches. In the cases treated since the fall of 1949, when a systematic procedure was first instituted, the aim was to administer 100 millicuries of I131 per month as long as evidence of tumor avidity for I131 could be shown.