We determined the magnitude of the pressor and sympathoexcitatory responses elicited by suprapontine cerebral ischemia (SCI) and the descending pathways in the rostral medulla mediating them. The suprapontine structures of anesthetized and artificially ventilated rabbits were selectively exposed to cerebral ischemia, by combined occlusions of basilar and common carotid artery. SCI produced a pressor response of 78 +/- 9 (SE) mmHg and an increase in renal sympathetic nerve activity of 289 +/- 21% compared with preischemic levels. The magnitude of the pressor and sympathoexcitatory response to SCI was comparable to those in response to global cerebral ischemia. Microinjection of the neurotoxin kainic acid into the pressor sites of the rostral ventrolateral medulla significantly (P < 0.05) reduced the SCI pressor response to 34 +/- 11% of the prelesion control response. Chemical lesions of the pressor sites in the rostral medial and ventromedial medulla resulted in a significant decrease in the pressor response to SCI to 78 +/- 12% of the control response. These results indicate that the suprapontine structures play an important role in the generation of the powerful pressor response elicited by cerebral ischemia and that the pressor response to SCI is mediated by pressor neurons in the rostral medulla.