Intravenous infusion of arginine vasopressin (AVP) has been shown to enhance baroreflex sensitivity, and this enhancement is dependent on the integrity of the area postrema. However, previous studies did not differentiate a role for cell bodies in the area postrema vs. the dense network of fibers located in and around the lateral and ventral margins of this circumventricular organ. In the present study, baroreflex function was assessed in conscious rabbits by examining heart rate after ramp infusions of phenylephrine (PE) and AVP. The subsequent day, the excitotoxin kainic acid was injected (30 nl initially, with five 15-nl supplemental injections of a 1 ng/nl solution over 1 h) into the area postrema, thus selectively destroying cell bodies. After an 8-day recovery period, baroreflex function was again assessed. The bradycardic response to graded infusion of PE (slope = -2.29 +/- 0.30) was not significantly different after selective lesions of area postrema neurons (slope = -1.88 +/- 0.49). In contrast, the previously enhanced bradycardic response to infusion of AVP (slope = -5.76 +/- 1.02) was significantly attenuated (slope = -2.31 +/- 0.21) to levels similar to that seen with infusion of PE. Thus selective chemical lesions of area postrema neurons block vasopressin-induced enhancement of the baroreflex.