The prolactin-releasing peptide (PrRP) has been proposed to be a co-transmitter or modulator of noradrenaline (NA) because it colocalises with NA in the A1 (in the ventrolateral reticular formation) and A2 (in the nucleus of the solitary tract; NTS) cell groups in the caudal medulla. The baroreceptor signals, originating from the great vessels, are transmitted primarily to the NTS, and then part of the signals is conveyed to the hypothalamic neuroendocrine neurones via the ascending NA neurones. The hypotensive haemorrhagic paradigm was employed to examine whether the PrRP-containing neurones in the caudal medulla participate in conveying signals to the hypothalamic neuroendocrine neurones. Among the caudal medullary A1 or A2 neurones, the majority of the PrRP-immunoreactive (-ir) neurones became c-Fos-ir at 2 h after hypotensive haemorrhage. Hypothalamic corticotrophin-releasing hormone-ir neurones and vasopressin-ir neurones became c-Fos positive in parallel with the activation of medullary PrRP-ir neurones. After delivery of retrograde tracer fluorogold (FG) to the paraventricular nucleus of the hypothalamus (PVN), part of the PrRP/FG double-labelled neurones in the A1 and A2 became c-Fos-ir after haemorrhage, demonstrating that PrRP-ir neurones participate in conveying the haemorrhagic stress-induced signals from the medulla to the PVN. PrRP and/or NA were microinjected directly to the PVN of conscious rats, and they presented a synergistic action on arginine vasopressin release, whereas an additive action was observed for adrenocorticotrophin release. These results suggest that the PrRP-containing NA neurones in the caudal medulla may relay the haemorrhagic stress-induced medullary inputs to the hypothalamic neuroendocrine neurones.