The discovery of a novel receptor-opioid receptor-like (ORL) receptor (1994) and its endogenous ligand-Orphanin FQ (OFQ) (1995) represented a new approach in the study of opioids and anti-opioids in CNS. Based on the high homology of ORL receptor and OFQ with their opioid family counterparts, as well as the high expression of ORL receptor mRNA and protein in the brain areas associated with nociception, the effect of OFQ on morphine induced analgesia in the rat brain was further investigated. The results showed that: (1) Intracerebroventricular (i.c.v.) injection of OFQ reversed the stress analgesia induced by i.c.v. injection of normal saline, which seems to be mediated by endogenous opioid peptides. (2) I.c.v. injection of OFQ dose-dependently antagonized morphine-induced analgesia dose-dependently. (3) I.c.v. injection of antisense oligodeoxynucleotide for the gene encoding ORL receptor to block the expression of ORL receptor in the CNS potentiated the analgesia induced by cumulative injection of morphine. The results suggest that OFQ seems to play a role of anti-opioid peptide in the rat brain.