The effect of amiodarone on thyroid hormone metabolism in heart, muscle, liver and kidney was investigated. Rats were treated ip with a high (100 mg.kg-1.day-1) or a low (50 mg.kg-1.day-1) dose of amiodarone for 10 days. Serum T3 was dose-dependently depressed (mean 30 and 54% of controls, respectively, p less than 0.01). rT3 was elevated (to 663 and 313% of controls, p less than 0.01 and 0.05, respectively). Serum T4 was depressed only in the high-dose group (to mean 80%, p less than 0.05). Tissue concentrations of T3 in the heart and muscle from treated animals did not differ from controls, whereas liver and kidney T3 contents were markedly reduced in both groups (p less than 0.05). Heart T4 and rT3 were elevated to about 200% of controls (p less than 0.01 and 0.05, respectively). The same pattern was observed in the other tissues. Iodothyronine-5'-monodeiodinase activity was significantly depressed in all tissues; heart: 32 and 28% of controls (p less than 0.05); muscle: 36 and 49% (p less than 0.01); liver: 11 and 13% (p less than 0.01); kidney: 22 and 28% (p less than 0.01), respectively. In conclusion, amiodarone depresses iodothyronine-5'-monodeiodinase activity in the heart, muscle, liver and kidney in a dose-dependent manner, resulting in lowered T3 concentrations in the liver and kidney, whereas no reduction of tissue T3 content is observed in the heart and muscle. This may indicate that T3 from plasma may cross the cardiac sarcolemma without hindrance.