A GREAT many studies have been carried out on the kinetics of iodine in man and a number of models have been proposed (1-9). The most common model has been a three-compartmental one in which iodine in the plasma is taken up by the thyroid and released back into the circulation as thyroid hormone. This in turn gets degraded and the released iodide recycles again. Excretion pathways from plasma iodide into urine and from plasma hormone into feces are also included.During the past ten years we have carried out over 100 kinetic studies on about 50 individuals in various states of thyroid function and found that the three-compartment model is inadequate to explain the data. In a previous publication (7), some of the computational problems encountered in connection with the data analysis were discussed and preliminary attempts to evolve a consistent model were presented. Further modifications of the model were introduced more recently. This paper is intended to summarize the present state of the model, the arguments for it and its shortcomings.The individuals studied included normals, hyperthyroids, euthyroids, hypothyroids and patients with thyroid cancers. Most of the individuals were studied at least twice, usually before and after various treatments. Treatments involved radioiodine therapy, hypophysectomy, and the administration of acetylated TSH.Several studies are chosen to show the spectrum of kinetic responses encountered (Fig. 1). These show both qualitative and quantitative differences in urine, thyroid and plasma responses for various perturbed states. Although it was possible to propose simple models to explain most of the studies individually, the models so derived were quite different from each other qualitatively. Since a "universal" model was sought to fit all the studies, the various features required in fitting the studies individually were integrated into a single model. The complexity of the proposed model evolved after efforts to derive a compatible, less complex model failed.Kinetic studies. The kinetic studies ranged in duration from about five to 30 days. Data were collected roughly in accordance with the schedule outlined below, although not all measurements were made in every study. All studies started with an iv injection of labeled iodide.The schedule of measurements was as follows: