Acute effects of lithium chloride (LiCl, 5 mEq./kg × 3), rubidium chloride (RbCl, 5mEq./kg×3), carbimazole (0.05 mEq./kg × 3) and short-term transfer stress on thyroid iodine metabolism were studied in rats fed a normal-iodine diet (NID). In addition, the effect of graded doses of LiCl (0–7.5 mEq./kg × 3) was studied in rats fed a low-iodine diet (LID). In the animals on NID carbimazole, LiCl and RbCl decreased the 4 h uptake of 131I. In chromatography it was found that only carbimazole and LiCl significantly decreased the synthesis of T3 + T4. Plasma TSH (radioimmunoassay) levels were slightly decreased by short-term transfer stress, RbCl and LiCl, but increased by carbimazole. In the animals on LID, the 131I uptake at 4 h decreased and correspondingly the plasma radioactivity increased with increasing doses and plasma concentrations of Li+. In chromatography the relative amounts of iodothyronines and DIT decreased, that of MIT increased, and the percentage of iodide remained unchanged. With a minimal effective dose, Li reduced only T4 and T3, with the higher dose DIT, then iodide and the total uptake of 131I, and lastly MIT. The plasma corticosterone level tended to increase and TSH level to decrease as the plasma Li concentration increased. Thus lithium in massive doses seems to be an antithyroid agent, its effects on thyroidal uptake and distribution of 131I resembling that of very small doses of propylthiouracil. The inhibitory effects of Li are dose-dependent. The decrease in plasma thyroxine level probably initiates the series of events which may lead to hypothyroidism, goitre or both conditions.