The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study, responses to intravenous injections of nociceptin were investigated in the systemic vascular bed of the rat. Nociceptin induced dose-related decreases in systemic arterial pressure and total peripheral resistance when injected in doses of 1-30 nmol/kg i.v.. Nociceptin decreased heart rate and in doses of 10 and 30 nmol/kg i.v., significantly decreased cardiac output. In terms of relative vasodilator activity, nociceptin was approximately 10-fold less potent than the beta-adrenergic receptor agonist isoproterenol. These data show that nociceptin has novel vasodilator activity in the systemic vascular bed of the rat.