Experiments were done in male Wistar rats to investigate the effects of microinjection of hypocretin-1(hcrt-1) into the nucleus of the solitary tract (NTS) on mean arterial pressure (MAP), heart rate (HR) and the baroreflex. In the first series, the distribution of hcrt-1 like-immunoreactivity (ir) was mapped within the region of NTS. Hcrt-1 ir was found throughout the NTS region, predominantly within the caudal dorsolateral (Slt), medial (Sm) and interstitial subnuclei of NTS. In the second series, in -chloralose or urethane anaesthetized rats, microinjection of hcrt-1 (0.5-5 pmol) into the caudal NTS elicited a dose-dependent decrease in MAP and HR. A mapping of the caudal NTS region showed that the largest depressor and bradycardia responses were elicited by hcrt-1 were from sites in the Slt and in the Sm. In addition, doses of >2.5 pmol at a small number of sites localized to the caudal commissural nucleus of NTS elicited pressor and tachycardia responses. Administration of the muscarinic receptor blocker atropine methyl bromide (iv) abolished the bradycardia response and attenuated the depressor response, whereas subsequent administration of the nicotinic receptor blocker hexamethonium bromide abolished the remaining MAP response. Finally, microinjection of hcrt-1 into t he NTS significantly potentiated the reflex bradycardia to activation of arterial baroreceptors as a result of increasing MAP by systemic injections of phenylephrine (2-4 µg/kg). These results suggest that hcrt-1 in the NTS activates neuronal circuits that increases vagal activity to the heart, inhibits sympathetic activity to the heart and vasculature, and alt ers t he excitability of NTS neuronal circuits that reflexly control the circulation.