Lorcainide, 100 mg twice daily was compared with placebo in 39 patients with frequent ventricular arrhythmias in a randomized double-blind crossover trial. A mean frequency of ventricular premature beats (VPBs) of at least 30 VPBs/hour was required during a drug-free period of 48 hours. Holter monitoring and a maximal symptom-limited exercise test were performed at the end of each of the 2-week double-blind treatment phase. The group averaged 350 +/- 361 (standard deviation) VPBs/hour. Lorcainide decreased the mean VPB frequency of the group by 46% (p less than 0.01), with VPB reduction beyond the expected variation in 22 of 39 patients. In 13 patients VPBs were unchanged and in 4 they increased. Eight additional patients responded during drug titration, for an overall response rate of 77% (30 of 39). Lorcainide did not significantly reduce the exercise-related VPB frequency. At 6 months 61% of patients had significant VPB suppression. Thus, lorcainide was effective in reducing the frequency and grade of spontaneous ventricular arrhythmias during short- and long-term evaluation.