Although we have demonstrated that amiodarone improve exercise capacity, reduces cardiac symptoms, and diminishes the frequency and severity of complex ventricular arrhythmias in patients with hypertrophic cardiomyopathy, its mechanisms of action have been poorly defined. Therefore, we studied 30 patients with hypertrophic cardiomyopathy using radionuclide angiographic techniques before and after loading dose (1200-1600 mg/day for 10 days) and maintenance dose (400-600 mg/day for 2 months) amiodarone. We examined left ventricular functional changes both during systole and diastole. Left ventricular rapid diastolic filling was assessed by examining the peak rate of LV filling and the magnitude of LV stroke volume filled during rapid diastolic filling. We found that the vast majority of patients manifested an improvement in both the rate and magnitude of rapid diastolic filling after initial amiodarone therapy. Although changes during maintenance amiodarone therapy were less striking, all patients in whomm the peak rate of filling or the magnitude of filling decreased compared to loading dose therapy also had reduced exercise capacity and worse cardiac symptoms. Thus, it appears that amiodarone improves diastolic filling characteristice in patients with hypertrophic cardiomyopathy and the changes in rapid diastolic filling parallel clinical status. This data suggest that improved rapid diastolic filling may be an important mechanism contributin to the clinical efficacy of amiodarone therapy in such patients.