The parasubthalamic nucleus (PSTN) projects extensively to the nucleus of the solitary tract (NTS), however the function of PSTN in cardiovascular regulation is unknown. Experiments were done in alpha-chloralose anesthetized rats to investigate the effect of glutamate (Glu; 10 nl, 0.25M) activation of PSTN neurons on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA). Glu stimulation of PSTN elicited depressor (-20.4 ± 0.7 mmHg) and bradycardia (-26.0 ± 1.0 bpm) responses, and decreases in RSNA (67 ± 17 %). Administration (iv) of atropine attenuated the bradycardia response (46%), but had no effect on the MAP response. Subsequent iv administration of hexamethonium blocked both the remaining bradycardia and depressor responses. Bilateral microinjection of CoCl₂ into the caudal NTS attenuated the PSTN depressor and bradycardia responses by 92% and 94%, respectively. Additionally, prior Glu activation of neurons in the ipsilateral NTS did not alter the magnitude of the MAP response to stimulation of PSTN, but potentiated the HR response by 35%. Finally, PSTN stimulation increased the magnitude of the reflex bradycardia to activation of arterial baroreceptors. These data indicate that activation of neurons in the PSTN elicits a decrease in MAP due to sympathoinhibition and a cardiac slowing that involves both vagal excitation and sympathoinhibition. In addition, these data suggest that the PSTN depressor effects on the circulation are mediated in part through the activation of NTS neurons involved in baroreflex function.