The quantitative aspects of iodine metabolism have been evaluated in normal healthy human subjects by means of a tracing method and long-term iodine balance studies. The behavior of the specific activities of hormonal iodine in the intra- and extra-thyroidal compartments cannot be explained on the basis of a relationship of precursor to product when the thyroidal compartments are considered as a whole. On the contrary, experimental findings fit with such a relationship if one considers the fraction of the thyroid compartment which is mobilized by exogenous TSH. A kinetic model of iodine metabolism taking account of such a functional heterogeneity has been studied by means of digital and analog computers. One interesting aspect of this heterogeneity is the very high specific activity of the organic iodine released by TSH, when TSH is given a short time after the administration of radioiodine. This. approach appears to be a very sensitive method for the detection of any TSH-like effect on the thyroid gland. This property has been used for the estimation of the influence of an acute exposure to cold on the thyroid function of eight volunteers. Twenty-four hours after the administration of I 125 the volunteers were kept for two hours at 4° C. A marked increase of the levels of PBI 125 was observed four hours after the end of cold exposure; plasma PBI 127 was also increased but to a lesser extent; the validity of these findings was checked by a parallel experiment at normal temperature. Stimulation of thyroid function thus appears as an immediate adaptative mechanism to cold, not only in the dramatic situations used in experimental studies, but also after short and relatively mild exposure, simulating conditions which are encountered ordinarily by many people living in cold countries.