Recent work has shown that alterations in the dynamic atrioventricular (AV) nodal response to changes in heart rate can significantly modify AV nodal function. The present study was designed to evaluate the nature and potential importance of sympathetic regulation of the rate-dependent properties of the AV node. Selective stimulation protocols and mathematical formulations were used to independently quantify AV nodal recovery, facilitation, and fatigue in 12 morphine-chloralose-anesthetized dogs. Vagal effects were prevented by bilateral vagal transection and intravenous atropine, and the sinus node was crushed to allow a broader range of pacing cycle lengths. In seven dogs with sympathetic nerves intact, β-adrenergic receptor blockade increased the recovery time constant (τrec) for the conduction of premature test beats from 47 ± 2 (mean ± SEM) msec (control) to 62 ± 1 msec (p < 0.001), whereas isoproterenol decreased τrecto 38 ± 1 msec (p<0.001). In addition, β-blockade increased the maximum amount of rate-dependent AV nodal fatigue from 7 ± 1 msec (at a cycle length of 198 ± 9 msec [control]) to 17 ± 2 msec (p<0.001). In five dogs with decentralized stellate ganglia, τrecwas decreased from 71 ± 3 msec (control) to 57 ± 4 msec and 48 ± 2 msec (p< 0.001 for each) by left stellate ganglion stimulation at 5 and 10 Hz, respectively. Maximum fatigue was similarly reduced from 16 ± 1 msec (control) to 12 ± 2 msec (p=NS) and 8 ± 1 msec (p<0.01), respectively. Stellate ganglion stimulation, isoproterenol, and β-blockade did not alter AV nodal facilitation. A mathematical model incorporating quantitative indexes of AV nodal function accurately accounted for tachycardia-dependent increases in the atrial-His activation interval, which were enhanced by β-adrenergic receptor blockade and reduced by isoproterenol. Furthermore, this model showed that β-adrenergic effects were increased by increasing heart rate, with the majority of the rate-dependent action being due to changes in the time course of AV nodal recovery. We conclude that β-adrenergic receptor stimulation alters functional properties that govern the AV nodal response to changes in heart rate. These changes in functional properties alter the ability of the AV node to conduct impulses during tachycardia and, as such, could play a major role in the ability of sympathetic stimulation to promote and β-adrenergic receptor blockade to prevent the occurrence of AV nodal reentrant arrhythmias. (Circulation Research1992;70:902–911)