Orphanin FQ (OFQ) is a novel peptide comprised of an amino acid sequence very similar to that of dynorphin A. In the present investigation the effect of OFQ on cardiovascular activities was studied. Introcerebroventricular (icv) injection of OFQ at doses of 1 and 10 micrograms produced significant decrease in heart rate (HR) and mean arterial pressure (MAP). Icv pretreatment with naloxone could not prevent the hypotensive and bradycardial response produced by 1 microgram OFQ. Injection of 1 microgram OFQ preoptic area (POA) also caused a profound decrease of MAP and HR. These results indicate that OFQ can inhibit cardiovascular activities which are not mediated by mu, delta and kappa receptors. POA may be one of the target areas of these inhibitory effects.