Lorcainide, a new antiarrhythmic drug, was given to 10 patients with frequent (greater than 1/min) premature ventricular contractions (PVCs) on a baseline 24-hour Holter monitor. Each patient received lorcainide, 100 mg twice daily, and an identical placebo, in a randomized double-blind crossover trial, with 1 week in each treatment period. Before the trial and at the end of each period, routine laboratory, clinical evaluation, 12-lead ECG's, and 24-hour ambulatory ECG recordings were performed. Trough drug plasma concentration measurements were done at the end of each treatment period. All patients had reduction in PVCs, comparing drug to placebo, averaging 82.3 +/- 19.7% (mean +/- SD, p less than 0.01 by Wilcoxin ranked sum), and there was also significant decrease in the number of ventricular pairs and runs. Levels of the major metabolite, norlorcainide, ranged from 34 to 254 ng/ml (mean 160 ng/ml) and exceeded those for lorcainide, range 6 to 169 ng/ml (mean 79 ng/ml). Prolongation of PR, QRS, and QTc intervals was evident during drug therapy, as was decrease in heart rate, but these changes were minimal. The major adverse effect noted was sleep disturbance, which was often initially severe, but improved during the week of therapy.