The protein-bound radioiodine and radioiodide concentrations in the thyroid gland and serum radioiodide concentrations in rats and mice were measured between 3 and 16 min after injection of radioiodide. The data were compared with predictions of a simple open three-compartment model of the thyroid gland. The model generally fitted the experimental data well. The amount of radioiodine incorporated into organic binding each minute varied from one-third to twice the amount of radioiodide in the thyroid, depending on diet. The data were also compared with previously published results on duplicate sets of animals in which the formation of protein-bound iodine was acutely blocked by a goitrogen. The ability of the thyroid to maintain a concentration of radioiodide elevated above that of blood serum was much less when binding was permitted than when blocked and seems to be due to removal of thyroid radioiodide by the binding process and, in addition in the rat, by increased transport of radioiodide from thyroid to blood.