To evaluate the antiarrhythmic effect of reflex-induced vagal activation, phenylephrine was infused in 17 patients with frequent ventricular premature complexes (VPCs). The role of heart rate reduction in suppressing VPCs was explored by pacing the atria at the preinfusion levels. Baroreceptor activation was considered effective when a greater than or equal to 20% decrease in heart rate was observed. Ten patients (59%) achieved the target heart rate decrease (-29 +/- 5%), whereas in 7 (41%) the baroreceptor reflex was considered inadequate. In the former group ("responders"), heart rate decreased from 73 +/- 7 to 52 +/- 6 beats/min (p less than 0.0001). When heart rate was allowed to fluctuate, ectopic activity was completely abolished in 9 of 10 patients; mean number of VPCs decreased from 38 +/- 8 to 0.2 +/- 0.6/100 beats (p less than 0.0001). During pacing, VPCs reappeared but their mean number (22 +/- 10/100 beats) was still significantly reduced compared with control values (p = 0.003). In the "nonresponders," despite adequate blood pressure increases, VPC frequency was not affected. The QT interval lengthened during phenylephrine (392 +/- 17 ms) versus control conditions (372 +/- 18 ms, p = 0.0008) in the responders group, whereas no change was observed in the nonresponders. These results demonstrate that reflex vagal activation markedly reduces VPCs. This effect is only partially rate-dependent; direct and indirect electrophysiologic changes secondary to baroreflex activation are also likely to be involved.