Besides the presence of goitrogens in the diet, the level of iodine itself in the diet plays a major role in governing the activity of the thyroid gland. In the experimental animal and in man gross deficiency in dietary iodine causes thyroid hyperplasia, hypertrophy and increased thyroid activity (Money, Rall and Rawson, 1952; Stanbury, Brownell, Riggs, Perinetti, Itoiz, and Del Castillo, 1954). In man the normal level of iodine in the diet and the level necessary to prevent development of goitre is about 100 | mg per day. With lower levels, thyroid hypertrophy and increased thyroid blood flow enable the thyroid to accumulate a larger proportion of the daily intake of iodine. Further, the gland is able to re-use a larger fraction of the thyroid hormone de-iodinated peripherally. In the presence of a low iodine intake, thyroglobulin labelled in vivo with ** f is found to contain more mono-iodotyrosine than normal, the amounts of di-iodotyrosine and iodothyronines being correspondingly reduced. This appears to result from both a reduced amount of the iodine substrate and a more rapid secretion of newly iodinated thyroglobulin. If the deficiency persists long enough, it is reasonable to suppose that the ** f label will reflect the ** f distribution in the thyroglobulin. Similar results might be expected from the influence of drugs or pathological conditions that limit iodide trapping, or organification, or accelerate thyroglobulin proteolysis.