Electrophysiological effects of 2 to 2.5 mg/kg iv disopyramide were studied in 10 patients with dual nodal pathways who used a slow pathway for anterograde and a fast pathway for retrograde conduction during paroxysmal supraventricular tachycardia (mean cycle length 308.5 +/- 37 ms; range 260-370 ms). Disopyramide terminated the tachycardia in six cases by production of ventriculoatrial block in five and by sinus overdrive in one. In the remaining four patients cycle length of the paroxysmal supraventricular tachycardia increased significantly from 270 +/- 8 ms to 377.5 +/- 28 ms. In all 10 patients disopyramide depressed retrograde fast pathway conduction manifest by an increase in mean ventricular paced cycle length producing ventriculoatrial block from less than or equal to 296.5 +/- 25 ms to 358 +/- 60 ms, and increase in retrograde fast pathway effective refractory period from less than or equal to 246 +/- 34 ms to 325 +/- 36 ms; the drug abolished ventriculoatrial conduction in two cases. Anterograde slow pathway and fast pathway conduction properties were unchanged after disopyramide (atrial paced cycle length producing AH block 292 +/- 30 to 306.5 +/- 30 ms; effective refractory period of anterograde fast pathway less than or equal to 274 +/- 56 to 284 +/- 44 ms, before and after the drug, respectively) suggesting that anterograde conduction was not crucial either for sustainment or for failure to initiate paroxysmal supraventricular tachycardia after the drug. Paroxysmal supraventricular tachycardia could not be reinduced in six cases after disopyramide. In the other four the ventricular paced cycle lengths producing ventriculoatrial block (318 +/- 41 ms) and effective refractory period of retrograde fast pathway (320 +/- 28 ms) were shorter than the cycle length of reinduced paroxysmal supraventricular tachycardia (367.5 +/- 35 ms) allowing perpetuation of the tachycardia. We conclude that disopyramide breaks atrioventricular nodal re-entrant tachycardia by specific blockade of the retrograde fast pathway though the effect on anterograde atrioventricular nodal conduction is variable.