The efficacy of disopyramide in the management of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) was evaluated in 50 patients by programmed ventricular stimulation: 38 patients had coronary artery disease (16 with left ventricular aneurysm), 8 had other cardiac diseases, and 4 had no apparent heart disease. Disopyramide was administered orally for 72 hours (dosage 400 to 1,600 mg/day), resulting in a plasma level of 3.6 +/- 1.2 micrograms/ml (mean +/- standard deviation [SD]). Disopyramide prevented induction of sustained ventricular tachyarrhythmias in 17 patients (34%) and failed to prevent induction in 33 patients (66%). Plasma levels were not significantly different regardless of response to disopyramide. The VT cycle length in patients responding to disopyramide was shorter than in nonresponding patients (225 +/- 51 ms versus 281 +/- 70 ms, p = 0.005). Disopyramide increased VT cycle length in those patients in whom it was ineffective (failed to prevent induction) from 281 +/- 70 ms to 347 +/- 64 ms (p less than 0.001). Ventricular refractory periods, QRS, and QTc durations significantly increased after disopyramide administration. Of the 17 patients in whom tachyarrhythmias were noninducible on disopyramide, 11 were discharged on disopyramide and followed up for 19 +/- 9 months; 9 of them remained free of VT. Heart failure developed in 2 of these patients. One other patient in whom disopyramide was ineffective had irreversible heart failure and died. It is concluded that disopyramide (1) prevents induction of ventricular tachyarrhythmias in one third of patients studied and remains clinically effective in approximately 80%, (2) is more frequently effective in rapid tachycardias, (3) prolongs the VT cycle length when ineffective, and (4) may produce marked hemodynamic embarrassment in patients with significant left ventricular dysfunction.