The efficacy and safety of combined amiodarone and mexiletine treatment was investigated in 16 patients with chronic complex ventricular arrhythmias previously refractory to conventional antiarrhythmic agents and, in a lesser degree, to mexiletine or amiodarone. Many patients had a poor left ventricular function. Oral amiodarone was started using a loading dose of 600 mg daily for one week, 400 mg daily for one week, and a subsequent dosage of 200 mg daily five times a week. After twenty-one days of this treatment mexiletine was administered in combination (600 mg/day orally), if a 24-hour ambulatory ECG had revealed a partial suppression of the ventricular arrhythmias (14 out of 16 patients). On the fourth day of combined amiodarone and mexiletine treatment, analysis of a 24-hour ambulatory ECG showed a marked diminution of the ventricular ectopic activity compared with the pretreatment period. The average percentages of reduction for PVCs and couplets were 88% and 97%. Total suppression of TV runs/24 hr was achieved in all patients. Ventricular arrhythmias relapse was found in all patients during early mexiletine washout (phase 4) and in 12 patients during late mexiletine washout (phase 5). Amiodarone and mexiletine combination did not appear to reduce left ventricular function. Minor side effects occurred in some patients. Follow-up from 3 months to two years (mean 16 months) showed that maintenance treatment had achieved remarkable antiarrhythmic effects (Holter control). However, sudden cardiac death occurred in two patients with very depressed left ventricular function. We conclude that a combined amiodarone and mexiletine treatment effectively reduces the frequency and grade of PVCs and does not impair left ventricular performance. However, it does not prevent sudden cardiac death in patients with poor left ventricular function.