In order to gain additional information on the role played by the opioids in the control of the secretion of anterior pituitary gonadotropins, morphine (an opioid agonist) and naloxone (an opioid antagonist) have been injected intraventricularly (i.v.t.) into normal or castrated male rats. The animals were killed by decapitation at different time intervals after treatment and serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured by radioimmunoassay. Animals injected i.v.t. with 0.9% saline solution and sacrificed at the same time intervals served as controls. When morphine (at the dose of 200 and 400 µg/rat) and naloxone (at the dose of 7.5 and 15 µg/rat) were injected i.v.t. into normal male rats, a significant increase of serum levels of LH was observed 10 and 20 min after injection. There was no effect at 5, 40 and 60 min. Lower doses of morphine (6.25, 12.5, 25, 50 and 100 µg/rat) given i.v.t. were ineffective. When morphine (200 µg/rat) and naloxone (either in the dose of 7.5 µg/rat or of 15 µg/rat) were given simultaneously, serum LH was significantly higher than in the saline-treated controls both at 10 and 20 min. However, the increases of serum LH levels induced by the combined treatment were in both instances lower than those produced by the administration of either drug alone. Morphine (200 µg/rat) when administered i.v.t. to normal male rats significantly enhanced prolactin release at 10 and 20 min, and this effect of morphine was blunted by the concomitant i.v.t. administration of naloxone (7.5 and 15µg/rat). Finally morphine, when injected i.v.t. in the dose of 200 µg/rat into male rats castrated 4 weeks before, significantly decreased serum LH levels beginning 40 min after treatment; this effect of morphine lasted up to the last interval of observation (180 min). No one of the subcutaneous or i.v.t. treatments discussed above exerted any consistent effect on serum FSH levels either in normal or castrated male rats. The following conclusions may be drawn from our observations: (1) The stimulatory effect exerted by naloxone given i.v.t. on LH secretion confirms that endogenous opioids exert mainly an inhibitory influence on LH secretion. (2) The stimulatory effect on LH secretion observed following the i.v.t. injection of morphine into normal male rats suggests that opioid pathways (or receptors) influencing in a stimulatory way the mechanisms controlling LH secretion might also exist. (3) The opposite effects exerted by i.v.t. morphine in normal and castrated male rats indicates that the endocrine ‘milieu’ present in the animal at the time of the experiment is crucial in directing the effects exerted by the opioids on LH secretion. (4) The lack of effect of morphine and naloxone on the release of FSH suggests that brain opioids do not participate in the regulation of the release of this gonadotropin. It appears from the data that the mechanisms controlling LH and FSH release are substantial