Spinal NMDA receptors contribute to control of the cardiovascular system by the ventrolateral medulla. However, little is known about the contribution of these receptors to suprabulbar regulation of hemodynamics and sympathetic outflow. Hence, the involvement of spinal NMDA receptors in regulation of the cardiovascular system by the paraventricular nucleus (PVN) of the hypothalamus was investigated. In urethane-anesthetized rats, the change in mean arterial pressure (MAP), heart rate (HR), and renal nerve activity (RNA) produced by electrical or chemical activation of the PVN was determined before and after intrathecal administration of the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (AP5). Intrathecal AP5 decreased resting MAP, HR, and RNA, but had no effect on the increase in RNA produced by electrical or chemical stimulation of the PVN. The pressor and renal vasoconstrictor effects resulting from electrical, but not chemical, stimulation of the PVN were significantly reduced by intrathecal AP5. These data show that much of the cardiovascular control exerted by the PVN does not depend on a spinal NMDA receptor mechanism.