Activation of excitatory N-methyl-D-aspartate and kainate receptors evokes multiple and diverse neuroendocrine changes. We have previously shown that kainic acid (KA), an agonist of kainate receptors, inhibits prolactin (PRL) secretion in male rats when given systemically. In the present studies we have characterized this inhibitory action. KA inhibited in vivo PRL secretion in neonatal, prepubertal and adult male rats. This inhibition was independent of gonadal secretion and was evident in male rats whether intact, orchidectomized, or orchidectomized and treated with testosterone. In addition, KA inhibited PRL secretion in male rats rendered hyperprolactinaemic by neonatal administration of oestradiol benzoate. The decrease in serum PRL levels after KA administration was accompanied by an increase in pituitary concentrations of dopamine, and the KA effect on PRL disappeared in males pretreated with domperidone, an antagonist of dopaminergic receptors. These findings strongly suggest that an increase in dopamine release was involved in the effects of KA. Also, KA inhibited in vitro PRL secretion by adenohypophysial dispersed cells and this effect was blocked by 6,7-dinitroquinoxaline, a kainate receptor antagonist, which indicates that the pituitary is also a possible site of action of KA. Nw-nitro-L-arginine-methyl ester, a blocker of nitric oxide synthase, reduced the effects of KA in vivo and slightly stimulated PRL release in vitro. We conclude that the inhibitory action of KA is independent of the age of the animal, the gonadal status and the prevailing PRL levels. The action of KA is probably mediated by an increase in dopamine secretion and by a direct effect at the pituitary level. Finally, the effect of KA on PRL secretion is partially dependent on endogenous nitric oxide.