The role of the central nervous system in the mechanism (s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcspwas reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcspof 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 ± 3.1 mm Hg and a set point pressure (Psp) of 104.7 ± 2.5 mm Hg. Increasing LCcspto 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pthand Psp increased by 18.4 ± 4.0 and 14.2 ± 3.0 mm Hg, respectively (< 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcspto 60 mm Hg caused Pthand Psp to decrease by 24.7 ± 5.0 and 18.1 ± 2 mm Hg, respectively (p<0.05). The baroreflex curve was therefore shifted downward and to the left. The percent of resetting of Pthand Psp was 46 ± 9% and 36 ± 8%, respectively, when LCcspwas 140 mm Hg. These values were 61 ± 14% and 46 ± 5%, respectively, when the LCcsp, was set to 60 mm Hg. These results show that conditioning of the ipsilateral carotid sinus baroreceptors can induce acute baroreflex resetting from the contralateral, unconditioned carotid sinus. This strongly suggests that the conditioning pressure can cause baroreflex resetting by a central mechanism alone without the need for the receptors themselves to be reset.