A B S T R A C T A method has been devised which is free of many of the shortcomings of serial epithyroid counting techniques as an index of the rate of thyroid hormone seeretion. By means of this method, the effect of treatment with Lugol's iodine on the rate of thyroidal secretion of thyroxine (T4) has been assessed in eight patients with thyrotoxicosis due to diffuse or multinodular goiter. The technique involves administration of a tracer dose of inorganic 'I followed several days later by an intravenous tracer dose of "'I-labeled T4. Serial observations of serum protein-bound (PB) 'I and 'I are accompanied by frequent measurements of endogenous serum T4 (T4-'I) concentration. Regardless of whether or not its administration was anteceded and accompanied by the administration of large doses of methimazole, iodine induced a rapid decrease in serum T4-RI concentration which could not be explained by an increase in the peripheral turnover of T., as judged from the metabolism of the "I-labeled hormone. Hence, the decreased serum T4 concentration could only have resulted from decreased secretion of the hormone by the gland. Analyses of specific activity relationships between PB'I or T4-1'I and PB1I made possible estimations of the extent to which iodine had decreased the rate of secretion of T4. From such analysis, and in view of other considerations, it is concluded that the rapid decrease in T4 secretion induced by iodine is not the result of an acute, sustained inhibition of T4 synthesis, but rather results from an abrupt decrease in the fractional rate of thyroidal T4 release.