The central pathway mediating the Bezold-Jarisch reflex elicited by jugular vein injection of serotonin (5-HT) and phenyl biguanide (PBG) was studied in halothane-anesthetized, paralyzed rats. 5-HT and PBG produced hypotension and inhibition of lumbar sympathetic discharge often preceded by sympathoexcitation. The Bezold-Jarish reflex was blocked by bilateral kynurenic acid (KYN; glutamate antagonist, 1.25 nmol/side) microinjection into the solitary tract nucleus. Bilateral KYN injection into the caudal ventrolateral medulla (5 nmol/side) also blocked the reflex. Bilateral injection of bicuculline methiodide (BIC; 100 pmol/side) into the rostral ventrolateral medulla (RVL) reduced the depressor and sympathoinhibitory components of the reflex and enhanced an excitatory component. Blockade or attenuation of the Bezold-Jarisch reflex was always associated with a concomitant blockade or attenuation of the arterial baroreflex. RVL barosensitive neurons (n = 61) were inhibited (> 60% reduction in firing) by PBG and 5-HT. Iontophoretic application of BIC (n = 11 cells), but not strychnine (glycine antagonist), blocked inhibition of RVL neurons by 5-HT and PBG. The sympathoinhibitory component of the Bezold-Jarisch reflex may use a central pathway similar to that of the arterial baroreflex.