Whether there is a link between the antiarrhythmic efficacy of amiodarone and its blocking effect on the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) is uncertain. If such a link exists, oral intake of T3 during amiodarone treatment could reverse, at least partially, the antiarrhythmic efficacy of amiodarone. To assess the safety of oral intake of T3 during amiodarone treatment and gain further insight into the relation between the antiarrhythmic action of amiodarone and its metabolic effect on T4, 7 patients (aged 32 to 62 years) with multiple ventricular premature complexes (VPCs) but no underlying heart disease were studied. Antiarrhythmic treatment was indicated for symptomatic relief only. Each patient underwent a 48-hour ambulatory electrocardiographic recording, electrocardiography and thyroid function tests, including plasma T4, T3, reverse T3 (rT3), free T4, free T3 and thyroid-stimulating hormone without treatment (baseline) after 1 month of amiodarone therapy and after a second month of amiodarone therapy with increasing doses of oral T3 (up to 75 micrograms/day). Treatment with amiodarone resulted in a decrease in plasma T3 and free T3, an increase in plasma rT3, a marked diminution in the frequency of VPCs and a prolongation of the corrected QT interval (QTc). During treatment with amiodarone and T3, plasma T3 and free T3 increased and plasma T4, free T4 and rT3 levels decreased; the frequency of VPCs remained low despite shortening of the QTc to values not different from baseline. Thus, in patients with frequent VPCs and no underlying heart disease, oral intake of T3 during amiodarone treatment is safe and does not abolish the antiarrhythmic efficacy of amiodarone, despite a shortening of the QTc.(ABSTRACT TRUNCATED AT 250 WORDS)