Myocardial size and contractility were measured by gated radionuclide ventriculography in 70 patients before and a mean of 66 days after beginning amiodarone therapy. The mean dose of amiodarone at the time of the second study was 481 mg. The mean left ventricular (LV) ejection fraction (EF) increased slightly, from 40% to 43% (p = 0.001). The mean right ventricular EF remained unchanged (38% to 39%, difference not significant [NS]). The LV end-diastolic volume (count-based method) increased by 9% (p = 0.01), but no change could be demonstrated for end-systolic volume (4%, NS). The LV stroke volume increased 19% (p = 0.001), but cardiac output remained unchanged (5%, NS) because the heart rate decreased by 9 beats/min (p = 0.001). The right ventricular end-diastolic volume increased by 12% (p = 0.01) and end-systolic volume increased by 11% (p = 0.03). Stroke volume increased by 18% (p = 0.005). There was no significant correlation between the change in LVEF and the pre-amiodarone LVEF, the time interval between studies, or with indexes of amiodarone effect (change in heart rate, QRS, QTc, TSH, amiodarone dosage). In 5 patients (7%), LVEF decreased significantly, requiring discontinuation of amiodarone therapy in 1 patient. At the time of the second study congestive heart failure was manifest in 19%, and there was a trend suggesting that congestive heart failure was more likely if the initial LVEF was less than or equal to 35% (p = 0.10). Thus, amiodarone may rarely adversely affect contractility, although myocardial contractility is typically unchanged. There is an associated small increase in the size of both ventricles.