Paroxysmal supraventricular tachycardia (PSVT) is likely due to reentry involving the atrioventricular (AV) node, AV node with AV bypass pathway, sinus node, or atria. Intravenous diltiazem (DIL) or verapamil (VER) might be used to treat PSVT in anesthetized patients, and either drug could be more or less effective or produce adverse circulatory effects in this circumstance because the available inhalation anesthetics are known to elevate plasma concentrations of acutely administered iv DIL or VER. Because human studies were precluded and there are no reliable animal models for most reentrant PSVT, the authors determined the effects of iv DIL or VER and potent inhalation anesthetics (enflurane, halothane, isoflurane) on supraventricular electrophysiologic (EP) properties affecting the likelihood of reentrant PSVT in chronically instrumented dogs. Measurements of supraventricular EP properties in awake dogs without drugs served as control. DIL and VER were then administered iv to achieve clinically relevant plasma concentrations in awake dogs and EP properties were again measured. Finally, anesthetic effects on EP properties in dogs with DIL or VER were tested at end-tidal concentrations equivalent to 1.2 or 1.6 MAC for enflurane, halothane, or isoflurane. In awake dogs, DIL or VER increased AV node conduction time, Wenckebach point and functional refractoriness, and also reduced the range of premature atrial intervals for and likelihood of producing sinus node interpolation or reentry with atrial extrastimulation (P< 0.05, ANOVA). AV node conduction time, Wenckebach point, and functional refractoriness were further increased in anesthetized dogs (all agents) with DIL or VER compared with control (P<0.05, ANOVA). All anesthetics with DIL or VER abolished sinus node interpolation and reentry. Atrial effective and functional refractory periods were not affected by DIL or VER in awake dogs and were increased by any of the anesthetics in dogs with DIL (P< 0.05, ANOVA). Atrial refractory periods were little affected by anesthetics with VER. Adverse circulatory effects, including systolic arterial pressure < 50 mmHg and second-degree (type 1) AV block or sinus arrest with escape rhythms, were most common with VER and any (especially enflurane) of the anesthetics. Finally, anesthetized animals with sinus arrest and escape rhythms (any test condition) could be paced from the atrium at physiologic rates (up to 120 beats/min). The authors conclude that with the potent inhalation anesthetics (iv DIL or VER should be effective against most reentrant PSVT), there is increased risk of adverse circulatory effects with VER compared with DIL, and sinus arrest or sino-atrial block (not complete AV block) is the mechanism for escape rhythms with either DIL or VER and anesthetics.