The aim of this study was to examine the cardiorespiratory effects of chemically stimulating neurons in the midline medulla oblongata (MM) of artificially ventilated, and freely breathing, anesthetized rats. Earlier studies reported that stimulation of the MM elicits increases or decreases in mean arterial pressure (MAP) and phrenic nerve activity (PNA) depending on the mode and site of stimulation, anesthetic used and species examined. In the first series of experiments, rats were anesthetized with urethane, artificially ventilated, paralyzed and bilaterally vagotomized. The rostrocaudal extent of the MM was mapped by microinjections of D,L-homocysteic acid or L-glutamate (both 100 mM, 100 nL), and in line with previous studies most injections produced only small responses in MAP, heart rate and splanchnic sympathetic nerve activity. Increases in respiratory parameters were evoked in caudal regions. However, activation of a discrete region of the MM at the level of the caudal pole of the facial nucleus (CP7) consistently caused a dramatic reduction in phrenic nerve amplitude and/or frequency, and in six rats produced a prolonged apnea. The second series of experiments was carried out on freely breathing pentobarbitone sodium anesthetized rats, using a diaphragmatic electromyogram to monitor respiratory activity. Respiratory activity could again be abolished at CP7 following microinjections of glutamate (100 mM, 50 nL), however these responses were accompanied by large decreases in MAP and moderate reductions in HR. This depression of respiratory activity may be due to the activation of propriobulbar inhibitory neurons that project to known respiratory centers in the brainstem.