Intravenous B-type natriuretic peptide (BNP) enhances the bradycardia of reflexes from the heart, including the von Bezold-Jarisch reflex, but its site of this action is unknown. The pep-tide is unlikely to penetrate the blood-brain-barrier, but could act on afferent or efferent reflex pathways. To investigate the latter, two types of experiment were performed on urethane-anesthetized (1.4 g/kg, i.v.) rats. First, activity was recorded extracellularly from single cardiac vagal motoneurons (CVM) in the nucleus ambiguus. CVM were identified by antidromic acti-vation from the cardiac vagal branch and by their barosensitivity. Phenylbiguanide (PBG), in-jected via the right atrium in bolus doses of 1-5 micrograms to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol/kg/min, i.v.) significantly enhanced both the CVM response to PBG (n=5 rats) and the reflex bradycardia, but the log-linear relation between those two responses over a range of PBG doses was unchanged by BNP. The reflex bradycardia was not enhanced in 5 matched time-control rats receiving only vehicle infusions. In 5 further rats the cervical vagi were cut and the peripheral right vagus was stimulated supramaximally at frequencies from 1-20 Hz. The bradycardic responses to these stimuli were unchanged before, during and after BNP in-fusion. We conclude that systemic BNP in a moderate dose enhances the von Bezold-Jarisch reflex activation of CVM, in parallel with the enhanced reflex bradycardia. That enhancement is due entirely to an action before the vagal efferent arm of the reflex pathway..