Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses in the rat. Central administration of CGRP activates the hypothalamo-pituitary-adrenal axis, specially enhancing corticosterone release. We have previously shown that central CGRP suppresses the gonadotropin-releasing hormone (GnRH) pulse generator, specifically LH pulses. Endogenous opioid peptides (EOP) have been shown to play an important role in stress-induced suppression of the reproductive axis and are additionally involved in various CGRP effects within the brain. The aim of the present study was to test the hypothesis that EOP mediate CGRP-induced suppression of pulsatile LH secretion. Wistar rats, anaesthetized with ketamine (100 mg kg^-1, ip) were ovariectomized and chronically implanted with intracerebroventricular (icv) and intravenous (iv) cannulae (ketamine, 100 mg kg^-1, ip). Blood samples (25μl) were collected at 5 min intervals for 6hrs for the detection of LH by radioimmunoassay. After 2 h CGRP (1.5 or 5μg/4μl) was administred icv either alone, or in addition to naloxone (250μg/200μl), given iv 10 min prior to CGRP injection (n=7-12). Additionally 1.5μg CGRP icv was co-administered after 2hr with naloxone (10μg icv), nor-binaltorphimine (nor-BNI, 5μg icv) or naltrindole (5μg icv), μ, κ and δ specific opioid receptor antagonists respectively (n=6-8). Controls received 4μl icv of artificial cerebrospinal fluid. The 1.5μg icv infusion of CGRP significantly (paired Student’s t test, p<0.05) prolonged the LH inter-pulse interval from 29.3±3.4 min (mean±sem) before treatment to 38.7±4.6 min after treatment (n=12). The higher dose (5μg CGRP) completely abolished LH pulses for the duration of the 4 h post-treatment period (n=8). Naloxone (250μg iv) completely blocked the inhibitory effects of 1.5μg CGRP on LH pulses in all rats treated, and significantly (paired Student's t test, p<0.05)attenuated the effects of 5μg CGRP. Co-administration of icv naloxone or nor-BNI completely blocked the inhibitory effects of 1.5μg CGRP on LH pulses whilst naltrindole did not. These data provide evidence that EOP play a pivotal role in mediating the inhibitory effects of CGRP on pulsatile LH secretion in the rat. The data also shows that the μ and κ, but not the δ, specific opioid receptors, are responsible for mediating the effects of CGRP on LH pulses.