Ventricular fibrillation occurred during Holter electrocardiographic monitoring in 5 of 3,307 consecutive patients. All five patients had Holter studies for evaluation of antiarrhythmic drug therapy; their ages ranged from 51 to 65 years. No patient had acute myocardial infarction; all had congestive heart failure and severe left ventricular dysfunction. One patient had ischemic and four had nonischemic cardiomyopathy. All patients had recently begun treatment with oral quinidine and had plasma quinidine levels of 1.24 to 5.18 microgram/ml. The Holter monitoring revealed that all had a long Q-T interval and that ventricular fibrillation began during frequent ventricular premature beats and was immediately preceded by ventricular tachycardia of the torsade de pointes type. The coupling interval of the ventricular premature beats initiating torsade de pointes was late (440 to 720 ms) and followed long preceding cycles (840 to 1920 ms). Ventricular fibrillation resolved spontaneously in two patients, but two of the remaining three patients died despite attempted cardiopulmonary resuscitation. It is concluded that (1) left ventricular dysfunction, chronic ventricular arrhythmias and initiation of quinidine therapy were the common findings in these patients; (2) a long Q-T interval, late coupled ventricular premature beats and long preceding cycles facilitate initiation of ventricular fibrillation in quinidine-treated patients; and (3) direct on-line monitoring should be utilized in the management of these patients.