Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the m-opiate receptor. In the present study, the effect of OFQ orrand endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i. c. v.) administration of OFQ (1,5μg) could shorten tail-flick latency; In contrast, intrathecal (i. t.) administration of OFQ (1, 2 or 10μg) could increase the latency; i. c. v. (1, 2, 5μg) or i. t. (0.2, 2, 5μg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5μg) when intraventricularly injected together with endomorphin-1 (5μg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1μg) intrathecally injected together with endomorphin-1 (0.2μg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested. © 1999 Elsevier Science B. V. All rights reserved.