The effect of varying doses of stable sodium iodide on thyroid hormone biosynthesis has been studied in rats. From measurements with 131I, the incorporation of iodine into several thyroidal components was determined, both as a proportion of the administered dose and as the absolute quantity of administered iodine. In short-term (30-min) experiments, 2 phases of response could be distinguished. Over a narrow range of small iodide doses, the proportionate metabolism of iodine remained unchanged. In this range, the percentage uptake and organification and the percentage incorporation of administered I31I into iodinated amino acids was unaltered. The total quantity of administered iodine accumulated and incorporated into mono- and diiodotyrosine and iodothyronines increased with and remained proportional to the dose of iodide administered. The second phase of iodine metabolism was induced by larger doses of iodide. Here, increasing doses led to progressively severe: 1) decrease in mI uptake, 2) decrease in proportionate organification of thyroidal iodide, 3) decrease in the proportion of diiodotyrosine and iodothyronines among the thyroidal iodinated amino acids and 4) decrease in the absolute rate of organic iodinations and iodothyronine synthesis. These changes are considered to be classic sequelae of an inhibition of the organification mechanism. Qualitative changes in the iodinated products formed, characteristic of the antithyroid effect, were independent of the absolute rate of organic iodinations, being absent when iodinations were increasing, and present when iodinations were decreasing, in response to increasing doses of iodide. It is concluded that, during the phase of increasing iodinations induced by increasing doses of iodide, the thyroid synthesizes increased quantities of hormonally active materials. The antithyroid effect of larger doses of iodide is evident over the entire range of decreasing iodinations and is independent of the absolute rate of organic iodinations. (Endocrinology74: 731, 1964)