Using an in-vitro superfusion system, the relative importance of three distinct subtypes of the opiate receptor in the control of the secretion of LHRH from the mediobasal hypothalamus of the cockerel was investigated. Basal release of LHRH was increased by the antagonist naloxone, which shows some mu-receptor selectivity, in a manner which was reversed by the mu-receptor specific agonist [D-Ala2, N-Phe4-Gly-ol5]-enkephalin (DAGO) and the mu- and delta-specific agonist [D-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824). The delta-specific agonist [D-Thr2,L-Leu5]-enkephalyl-Thr (DTLET) and the kappa-specific agonist 1-methyl-2(3-thienylcarbonyl)-aminomethyl-5-(2-fluorophenyl)-H-2, 3-dihydro-1,4-benzodiazepine (KC 6128; (+)-titfluadom) did not reverse the effect of naloxone. The delta-specific antagonist N,N-diallyl-Tyr-alpha-aminoisobutyricacid-Phe-Leu-OH (ICI 174,864) failed to influence basal release. Release of LHRH stimulated by increasing the potassium ion concentration of the superfusate to 48 mmol/l was reduced by DAGO in a manner which was reversed by naloxone, and by FK 33-824 in a manner which was reversed by both naloxone and ICI 174,864. The agonists DTLET and titfluadom did not affect stimulated release of LHRH. These results support the proposal that spontaneous release of LHRH is tonically inhibited by agonists acting through the mu-receptor whilst, in response to a stimulus, the delta-receptor, in addition to the mu-receptor, may be involved.