We have previously shown that P_2x purinoceptor activation in the subpostremal nucleus tractus solitarius (NTS) produces dose-dependent decreases in mean arterial pressure (MAP), heart rate, efferent sympathetic nerve activity, and significant peripheral vasodilation. However, the relative roles of cardiac output (CO) and total peripheral resistance (TPR) in mediating this depressor response are unknown. Bradycardia does not necessarily result in decreased CO, because, with the greater filling time, stroke volume may increase such that CO may be unchanged. We measured changes in CO (via a chronically implanted flow probe on the ascending aorta) and MAP in -chloralose- and urethane-anesthetized male Sprague-Dawley rats in response to microinjection of the selective P_2x purinoceptor agonist ,-methylene ATP (25 and 100 pmol/50 nl) into the subpostremal NTS. TPR was calculated as MAP/CO. At the low dose of NTS P_2x purinoceptor agonist, the reduction in MAP was primarily mediated by reductions in TPR (31.3 ± 3.3%), not CO (8.7 ± 1.7%). At the high dose, both CO (34.4 ± 6.6%) and TPR (40.2 ± 2.5%) contribute to the reduction in MAP. We conclude that the relative contribution of CO and TPR to the reduction in MAP evoked by NTS P_2x purinoceptor activation is dependent on the extent of P_2x purinoceptor activation.