Microinjection of glutamate into sites within the medullary raphe nuclei (pallidus and obscurus) at levels caudal to the obex resulted in a dose-dependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate in anesthetized rabbits. The depressor and sympathoinhibitory responses were similar in magnitude to those elicited from the previously described depressor region in the caudal ventrolateral medulla (CVLM) but had a shorter duration, in both intact and barodenervated animals. The bradycardia was not altered by barodenervation but was reduced after administration of propranolol or atropine and abolished after administration of both drugs. The neuroinhibitory compounds gamma-aminobutyric acid or muscimol had no effect on MAP or RSNA when injected into the caudal medullary raphe nuclei but evoked a pressor and sympathoexcitatory response when injected into the CVLM. The results indicate that neurons within the caudal raphe pallidus and obscurus can powerfully inhibit sympathetic activity, but unlike sympathoinhibitory neurons in the CVLM, they are not tonically active and are not capable of producing sustained changes in arterial pressure and sympathetic activity.