We evaluated plasma PRL and LH concentrations in the rat after the administration of drugs that exert a specificity directed mainly, although not absolutely, toward the mu-, delta-, or kappa-opiate receptors, in order to investigate the role of different receptors and thus the respective endogenous ligands in the modulation of the release of these anterior pituitary hormones. LH concentrations were evaluated in prepuberal female rats, in adult male rats, and in ovariectomized, estradiol benzoate-treated rats. PRL concentrations were evaluated in suckling rats, in ovariectomized, estradiol benzoate-treated rats, and in ether-stressed rats. The delta-antagonist ICI 154129 never affected PRL or LH concentrations, whereas both the mu- and kappa-antagonists, naloxone and MR 1452, respectively, seemed to be effective. However, when graded doses of the two classes of antagonists were tested, the mu-antagonist appeared to be effective on both hormones at doses that were one tenth of those of the kappa-antagonist. In conclusion, the mu-receptor seems to be the most profoundly involved in the regulation of PRL and LH secretion.