A prospective study was conducted on 10 normal male volunteers to investigate the effect of the administration of excess iodide on thyroid volume. After 1 week of dietary iodide restriction, all subjects were given daily oral doses (27 mg daily total iodine dose) of licorice lecithin-bound iodine tablets for 4 weeks. Thyroid function studies, total serum iodine concentration, and urinary iodine excretion were monitored. Thyroid volume was measured by high resolution echoscanner before treatment, on the day of the last treatment, and 1 month after the treatment. There was a significant rise in serum TSH levels, with a small decline in serum free T4 concentration during iodide administration; the values remained within the normal range except for two subjects. Serum thyroglobulin levels were increased in parallel with serum TSH levels, which became higher than normal after 1 week of treatment. The volume of the thyroid gland became significantly enlarged after 28 days of iodide intake. When iodide was discontinued, thyroid volume and function returned to baseline levels within 1 month for all subjects. This is the first documentated objective evidence that the compensatory rise in serum TSH in response to iodide administration elicits reversible thyroid hypertrophy in normal subjects.