The provocation or worsening of arrhythmias by antiarrhythmic regimens was evaluated in patients with malignant ventricular arrhythmias undergoing electrophysiologic studies. In 314 patients with sustained or nonsustained ventricular tachycardia or ventricular fibrillation, 801 drug studies were performed using a standard protocol of programmed electrical stimulation. The criteria for proarrhythmia were: 1) initiation of sustained ventricular tachyarrhythmia in a patient in whom only nonsustained tachycardia was induced at baseline; 2) conversion of a sustained tachycardia that could be terminated by programmed electrical stimulation at baseline to one that required cardioversion for termination during drug therapy; 3) initiation of a sustained tachyarrhythmia by a less aggressive mode of stimulation than was required at baseline; and 4) development of spontaneous or incessant ventricular tachycardia. Proarrhythmia criterion 1 occurred during 20 (18%) of 118 studies and at least once in 15 (28%) of 54 patients. Criterion 2 was met during 39 (7%) of 578 studies and at least once in 29 (13%) of 220 patients. Criterion 3 was achieved during 135 (20%) of 687 studies in patients with sustained ventricular tachyarrhythmias at baseline. Criterion 4 occurred during 9 (1%) of 801 drug studies. In 40 patients in whom well tolerated ventricular tachycardia was initiated with fewer extrastimuli during drug study than at baseline, the drug was continued and the patients were followed up. The recurrence rate of tachycardia was the same in these patients as in 73 patients followed up on regimens on which the number of extrastimuli required for initiation was not reduced.(ABSTRACT TRUNCATED AT 250 WORDS)