Both hyperthyroidism and hypothyroidism have been noted to occur in some patients treated with amiodarone for cardiac arrhythmias. To determine the frequency of the development of thyroidal abnormalities in patients receiving amiodarone, 45 euthyroid patients were prospectively evaluated. Serum samples were obtained for measurement of thyroxine, thyrotropin, triiodothyronine, and triiodothyronine resin uptake prior to initiation of amiodarone treatment and serially over a 12- to 27-month period during which amiodarone was administered. The patients were divided into four subgroups as follows: Group I (n = 22) had elevated thyroxine levels, Group IIA (n = 13) had normal thyroxine levels and normal thyrotropin levels, Group IIB (n = 7) had normal thyroxine levels and elevated thyrotropin levels, and Group III (n = 3) had subnormal thyroxine levels. Demographic factors (such as route of administration, cardiac diagnosis, sex of the patient, or indication for amiodarone therapy) and amiodarone levels had no significant effect on the thyroid hormone parameters. However, Group I patients were statistically older than the patients in the other groups. Linear regression analysis revealed a negative correlation for thyroxine levels and a positive correlation with thyrotropin levels with age for the whole group. The various groups were not statistically affected by duration of therapy, but a positive trend existed for increasing thyroxine levels. Although virtually all patients showed changes in their thyroid hormone levels, chemical hyperthyroidism (elevated thyroxine and triiodothyronine levels without symptoms) developed in only two patients (4 percent), and clinical hyperthyroidism (elevated thyroxine and triiodothyronine levels with symptoms) developed in no patients. Four patients (9 percent) became biochemically and clinically hypothyroid. Thus, amiodarone frequently influences thyroid hormonal parameters, but less commonly causes a change in actual thyroid function. However, hyperthyroidism and hypothyroidism do occur in a significant number of patients.