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Using the rat and guinea-pig as an experimental animal model, the effect of amiodarone (Cordarone) on normal of hyperplastic thyroid was investigated in eu- or hypothyroid animals. Following short- or long-term treatments with different doses of amiodarone (5-50 mg/day) and amiodarone-equivalent amounts of stable iodine, serum thyroid hormones were assayed, followed by determination of thyroid uptake of radioiodine, the weight of the thyroid gland and its histological structure. Having received amiodarone chronically, euthyroid rats showed decreaed levels of serum T3 and T4, in contrast to euthyroid guinea-pigs in which no appreciable differences between amiodarone-treated and untreated animals were observed. However, the weight of the thyroid decreased in both species after amiodarone treatment. A similar effect was seen after the treatment with excessive iodine, but only in euthyroid rats, while the guinea-pigs showed increased gland weight and activation of the follicular epithelium, as seen on histological sections. These differences obeserved in thyroid glands of rats and guineapigs were probably associated with the facts that the normal dietary iodine intake was lower in guinea-pigs and their thyroid glands were more sensitive to excess of iodine than that of rats. After chronic amiodarone treatment, hypothyroid rats with hyperplastic thyroids showed a much greater increase of serum T4 than the control rats, while the T3 increase was appreciably smaller. After several months (5 and 6.5) of amiodarone treatment, the appearance of various lesions was observed in the thyroid follicular epithelium of these animals. These microlesions probably resulted in a direct toxic effect of amiodarone on the hyperplastic gland. The results of the present investigation suggest that amiodarone effects on the thyroid may not be associated with excessive iodine exclusively, but also with the specific effects of amiodarone on this gland.