Recent studies have shown that rapid atrial activation causes atrial electrical remodeling (AER), which recovers quickly following withdrawal of stimulation. The underlying mechanisms, however, are incompletely understood. The purpose of the present study, therefore, was to characterize the effect of the vagus on AER as well as define possible mechanisms of the phenomenon. Eight dogs were used in the study for 3 consecutive protocols. In the first, the dogs were subjected to atrial pacing at 800 ppm for 7 hours. Every hour, pacing was interrupted for a short time and atrial effective refractory period (AERP) was measured at 6 sites. The rapid atrial pacing was then discontinued and the electrophysiological study was repeated every hour for another 7 hours. Time-domain parameters of heart rate variability (HRV) were also computed 1 hour before pacing as well as each of 7 hours after the rapid atrial pacing protocol. The second program was performed two weeks after the first; 0.04 mg/kg of atropine was administered intravenously 30 min before pacing, and then 0.007 mg/kg was added at each hour. Parameters of HRV were not evaluated. Finally, the 8 dogs were subjected to the third protocol 2 weeks after completion of the second; 0.2 mg/kg of propranolol was given intravenously 30 min before pacing, and 0.04 mg/kg was added at each hour. The dispersion of AERP (dAERP) was calculated as, maximum AERP minus minimum AERP. There was a prompt decrease in AERP as the result of pacing (P<.05), but dAERP did not change significantly. The AERP recovered quickly, and dAERP increased from 21 +/-5.3 ms to 40 +/- 7.4 ms (P<.05) after cessation of pacing. At the same time, the parameters of HRV increased (P<.05) after cessation of pacing. The AERP increased from 128 +/- 12 ms to 135 +/- 12 ms and from 127 +/- 12 ms to 142 +/- 14 ms (P<.05) after vagal and autonomic blockade. However, AERP decreased during pacing (P<.05) with vagal or autonomic blockade, but dAERP did not change significantly during or after pacing. These results suggest that vagal and autonomic blockade can not prevent AER, but a high vagal tone is associated with a high dAERP during recovery from AER, indicating that the vagus and sympathetic have a synergistic effect on the refractory period.