To prospectively determine the clinical efficacy and electrophysiologic effects of encainide in atrioventricular nodal reentrant tachycardia (AVNRT), 49 patients refractory to 2.7 +/- 1.5 previous antiarrhythmic drug trials underwent electrophysiologic study before and 47 did so after administration of oral encainide (75 to 240 mg/day). Encainide prolonged the minimum atrial pacing cycle length maintaining 1:1 atrioventricular (AV) nodal conduction from 334 +/- 55 to 391 +/- 55 ms (p = 0.0001). Encainide induced ventriculoatrial (VA) block in 12 patients (25%) and slowed the minimum ventricular pacing cycle length maintaining 1:1 VA conduction from 315 +/- 46 to 485 +/- 89 ms (p = 0.0001) in the remaining 35 patients. After encainide, AVNRT was not inducible in 32 of 47 patients (68%) primarily because of the effects on retrograde AV nodal conduction. In the remaining 15 (32%) patients, AVNRT remained inducible; however, the tachycardia cycle length slowed from 397 +/- 86 to 492 +/- 90 ms (p = 0.0001). There was no significant difference in the baseline minimum ventricular pacing cycle length maintaining 1:1 VA conduction in patients whose inducible tachycardia was or was not suppressed. Forty-seven patients were treated for 18.9 +/- 12.9 months (range 1 to 50) with oral encainide. Encainide was completely effective in eliminating recurrences of supraventricular tachycardia in 26 of 47 patients (55%) and partially effective in an additional 42%. Recurrences of arrhythmia occurred in 15 of 32 patients (47%) whose inducible tachycardia was suppressed by encainide and 7 of 15 patients (47%) whose inducible tachycardia was not suppressed by encainide (p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)