To test whether increased difficulty in inducing ventricular tachycardia during antiarrhythmic therapy can be considered a sufficient criterion for predicting long-term efficacy of such therapy in patients with ventricular tachyarrhythmias, 95 patients were studied with a graded stimulation protocol (single and double premature stimuli during sinus rhythm and ventricular drives of 120, 140, 160 and 180 beats/min). After a control study, the effects of oral antiarrhythmic drugs on the ability to induce ventricular tachycardia were assessed. The median number of drug trials was four per patient. After antiarrhythmic therapy, four subgroups of patients were identified. In 36 patients, there was no change in inducibility (group 1), whereas in 18 patients ventricular tachycardia was rendered more difficult to induce; that is, a sustained ventricular tachycardia was inducible at a basic drive at least 40 beats/min faster than during the control study (group 2). In 34 patients, ventricular tachycardia induction was suppressed (group 3) and in 7 patients with nonsustained ventricular tachycardia, only 3 to 5 repetitive ventricular responses were induced after treatment (group 4). During follow-up of 15.5 +/- 11.5 months, 10 patients of group 1 had a recurrence of ventricular tachycardia and 6 died suddenly, whereas in group 2 only 1 patient died suddenly and in group 3, 2 patients had a recurrence of ventricular tachycardia (group 1 versus 2 and 3, p less than 0.001, Mantel-Cox and Breslow; group 2 versus 3, no difference). Thus, increased difficulty in inducing ventricular tachycardia is a sufficient criterion for predicting long-term efficacy of an antiarrhythmic drug regimen.