In 65 patients a single oral dose of amiodarone (30 mg/kg) produced an antiarrhythmic effect on supraventricular or ventricular arrhythmias within 3 to 8 hours and lasted for 17 to 19 hours. On the second day a 15-mg/kg dose reproduced this effect within 3 to 9 hours. Plasma concentration of amiodarone increased to a maximum (2.2 ± 1.7 mg/ liter) (mean ± standard deviation) at 6 ± 3.5 hours and plasma levels of N-desethylamiodarone (NDA) rose to 0.2 ± 0.08 mg/liter at 12 ± 6.4 hours. Sixty-one other patients were given a single 30-mg/kg dose 7 hours to 4 days before open heart surgery. Biopsies of the right atrial and left ventricular walls were taken during surgery. Myocardial concentration of amiodarone was maximal in the atrium after 7 hours (13 ± 8 mg/kg) and in the ventricle after 24 hours (17 ± 11 mg/kg). NDA myocardial concentration increased progressively until 24 hours and then remained stable over 4 days (1.5 mg/kg). The amiodarone myocardial to plasma concentration ratio was similar in the atrium and in the ventricle and averaged 22 and 10 for amiodarone and NDA, respectively. A significant relation existed between amiodarone concentration and the effect on ventricular premature complexes (r = 0.74, p < 0.001) and between amiodarone plasma concentration and the effect on the atrioventricular conduction (r = 0.58, p < 0.001). The plasma concentration of amiodarone corresponding to a 60% decrease in arrhythmias averaged 1.5 to 2 mg/liter. These data suggest that the antiarrhythmic effect of a single 30-mg/kg oral dose of amiodarone can be achieved within hours for an amiodarone plasma concentration of 1.5 to 2 mg/liter and a myocardial concentration of 10 to 20 mg/kg. © 1985.