Antiarrhythmic drugs occasionally facilitate, rather than prevent, ventricular tachycardia. The purpose of this study was to assess the incidence of procainamide facilitation of ventricular tachycardia initiation during programmed electrical stimulation in patients with no history of spontaneous sustained ventricular tachycardia but who are at high risk. Twenty patients with advanced heart failure (mean left ventricular ejection fraction 0.19 +/- 0.09) and nonsustained ventricular tachycardia and in whom sustained ventricular tachycardia was not inducible by programmed electrical stimulation in the basal state were studied. Six patients had coronary artery disease, 13 had idiopathic dilated cardiomyopathy, and 1 had valvular heart disease. All patients received programmed stimulation from the right ventricular apex with one to three extra-stimuli before and after the intravenous infusion of 10 mg/kg of procainamide (serum level 6.6 +/- 2.4 mcg/l). In two patients (10%) sustained monomorphic ventricular tachycardia was initiated only after the administration of procainamide. One of these patients later died in ventricular tachycardia during hyperkalemia. Of the noninducible patients, during a follow-up period of 6 +/- 5 months, two died suddenly and one developed symptomatic ventricular tachycardia. Thus, procainamide can unmask potential reentry circuits in some patients who have not had spontaneous sustained ventricular tachycardia. In patients with heart failure, this risk, as assessed by programmed stimulation after a single dose of procainamide, appears to be low.