The antiarrhythmic efficacy of moracizin HCl (Ethmozine), a new oral phenothiazine derivative, was evaluated in 20 patients with chronic high-frequency ventricular arrhythmia confirmed by multiple ambulatory electrocardiographic recordings. Comparison with 72 +/- 24 hours (+/- standard deviation) of ambulatory recordings on moracizin treatment (average dose 295 +/- 58 mg 3 times daily or 9.8 +/- 1.0 mg/kg/day) was made. Maximal treadmill exercise provocation of arrhythmia and echocardiographic studies to detect effects on left ventricular function were also compared. The group had an average of 378 +/- 97 ventricular premature beats (VPBs) per hour while receiving placebo, with a mean VPB grade of 3.4 +/- 1.1 (modified Lown). When the patients received moracizin HCl, VPB frequency was reduced 53% (p less than 0.01), to a mean VPB grade of 2.2 +/- 1.4 (p less than 0.05). Seventy percent of the patients (14 of 20) showed a reduction in VPB frequency that exceeded the maximal expected variation; in 3 the frequency did not change and in 3 it increased with moracizin HCl. Resting electrocardiographic changes consisted of modest prolongations of PR interval (0.03 second) and QRS duration (0.02 second); however, QT prolongation was not observed. Heart rate and blood pressure at rest and peak exercise, exercise-related arrhythmia, exercise durations and echocardiographic measures of left ventricular function were unchanged by moracizin HCl compared with placebo. Side effects of moracizin++ HCl at these dosages were minimal (diarrhea in 1 patient, dizziness in 1 and diaphoresis in 1), although 2 patients tested at higher dosages had sustained ventricular tachycardia that may have been related to moracizin HCl.(ABSTRACT TRUNCATED AT 250 WORDS)