The Cardiac Arrhythmia Pilot Study, sponsored by the National Heart, Lung, and Blood Institute, is a multicenter, prospective, randomized, double-blind trial designed to identify patients having 10 or more ventricular premature complexes (VPCs) per hour within 6 to 60 days of acute myocardial infarction. The present investigation selected patients after acute myocardial infarction who had ambulatory electrocardiographic qualifying arrhythmia for CAPS. An additional baseline electrocardiogram was recorded before enrollment in the study to assess baseline spontaneous variability of VPCs. A total of 88 patients (15 women, 73 men, aged 57 +/- 10 years) were studied. The 43 patients (49%) receiving beta-blocking drugs were included because the dose was not altered between the 2 consecutive electrocardiographic recordings. This investigation shows that a 95% reduction in VPCs is required to document a significant drug effect rather than variability alone if 1 day of control and 1 day of treatment electrocardiographic recording are compared. Similarly, based on 1 day of electrocardiographic recording before and after antiarrhythmic therapy, 1,780% increase in VPC frequency is required to establish "arrhythmia aggravation" from an antiarrhythmic drug rather than from variability alone based on a 95% confidence interval. Variability of ventricular arrhythmias is independent of left ventricular function, whereas patients taking beta-blocking therapy tend to have greater VPC variability (p = 0.052), even though VPC frequencies were lower (59 +/- 19 vs 138 +/- 31 VPCs/hour, p less than 0.006) than those not taking beta-blocking drugs.