L-glutamate (GLU) or acetylcholine (ACh) injected into the nucleus tractus solitarii (NTS) of rat elicits a decrease in arterial pressure (AP) and heart rate (HR) similar to that seen with activation of the baroreflex. Both compounds may play a role in the mediation of the baroreflex at the level of NTS. The baroreflex may be disturbed in the spontaneously hypertensive rat (SHR). Thus we sought to determine if the dose-related responses to microinjection (50 nl) of the two putative transmitters into NTS may be altered in SHR vs Wistar Kyoto (WKY) controls. Both GLU and ACh produced significant dose-related decreases in AP and HR in SHR and WKY. The dose-related changes in AP elicited by GLU were shifted significantly to the right in SHR compared to WKY. Responses of AP were only different after intermediate doses of ACh. The dose-related HR responses to GLU were the same in SHR and WKY. However, the HR response to ACh was significantly reduced in the SHR. These data suggest that cardiovascular regulation in the NTS through GLU and ACh mechanisms may be disturbed in the SHR.