A possible functional relationship between endogenous opioid peptides (EOPs), corticotropin-releasing hormone (CRH) and excitatory amino acids (EAAs) in the control of LH secretion was investigated in ovariectomized estrogen-primed rats. An intraventricular (icv) injection of an EAA agonist, N-methyl-D-aspartate (NMDA), or an EOP antagonist, naloxone, produced an abrupt increase in the serum LH level. While icv pretreatment of the animals with 2-amino-5-phosphonovaleric acid, a specific NMDA receptor antagonist, did not affect by itself basal LH levels, it significantly suppressed the NMDA-induced and also the naloxone-induced LH release. An icv injection of CRH also interfered with the naloxone-induced LH release. However, the NMDA-induced LH release was not affected by an icv injection of CRH or of beta-endorphin. These results suggest that the sites of EOP and CRH inhibition may be located upstream of the site of NMDA stimulation on the GnRH neuronal pathway, and that CRH can inhibit LH secretion without mediation by EOP neurons.