Phenylephrine infusion (PE) has been used to raise arterial pressure (BP) in order to investigate reflex responses mediated by sinoaortic baroreflexes (SAB). Increases in cardiac filling pressures have been reported during PE. Our experiments determined whether PE selectively activates SAB without activation of vagal cardiopulmonary baroreflexes (CPR). We measured changes in mean BP, mean pulmonary arterial pressure (PAP), and renal sympathetic nerve activity (RSNA) during PE in alpha-chloralose-anesthetized dogs before and after sinoaortic denervation (SAD; n = 10), selective vagotomy (n = 9), or SAD and vagotomy (n = 4). PE elevated both BP and PAP in all dogs studied. In dogs with SAB and CPR intact, RSNA was reflexively inhibited (% change RSNA: -76.3 +/- 4.7). In SAD dogs, inhibition of RSNA was significantly attenuated but not abolished (% change RSNA: -27.5 +/- 11.8). This inhibition after SAD correlated closely with increases in PAP. Small BP changes (10 mmHg) were associated with insignificant changes in PAP and RSNA. Volume expansion after SAD produced changes in PAP and RSNA similar to those produced by PE. After selective vagotomy, the sensitivity (% change RSNA/mmHg change BP) of the reflex elicited by PE was significantly decreased (-2.7 +/- 0.03 pre vs. -1.8 +/- 0.12 post; P = 0.01). PE failed to change RSNA after combined SAD and vagotomy. We conclude that vagal CPR contribute to reflex inhibition of RSNA during PE except when elevations of BP are small.