Moricizine (ethmozine), a phenothiazine-related new antiarrhythmic agent previously used thrice daily, was studied to determine whether a twice daily regimen could be used with the same degree of efficacy and safety. Ten patients entered a single-blind, 35-day, placebo-controlled, outpatient longitudinal, crossover comparison using 10 to 12 mg/kg/day of moricizine. There were five 7-day phases in which the first, third, and fifth were placebo dosing and the second and fourth were randomized as to moricizine dosage regimen (every 8 hours vs every 12 hours). There were no statistically significant differences between the three placebo periods in ventricular premature complex (VPC) frequency. There was no statistically significant difference between the two dosing regimens for ventricular arrhythmia control with the first day of moricizine dosing; however, when averaging the sixth and seventh days on drug, there was a significantly greater reduction in frequency on the every 12 hour regimen compared to the every 8 hour regimen (p = 0.004). No relationship was found between the percent arrhythmia suppression and dose or plasma concentration. Six patients had transient side effects on the every 12 hour regimen vs four patients with side effects on the every 8 hour regimen. This study demonstrates that moricizine may be used every 12 hours with excellent efficacy and tolerance.