Many studies suggest that the hypothalamic opiate system modulates the secretion of LH and prolactin (PRL) by its effects on catecholamine release. We previously provided evidence that the LH response to the opiate receptor antagonist naloxone (NAL) may depend upon spontaneous activity in the hypothalamic noradrenergic system at the time the drug is administered. Thus, when NAL is given to rats which have low turnovers of hypothalamic norepinephrine (NE), only small transient rises in LH occur. This is contrasted to the effects of NAL on the LH responses of animals with high rates of NE turnover where marked amplification of phasic LH release is observed. In the present studies, we examined the effects of NAL on LH and morphine on PRL responses in androgen-sterilized rats (ASR). These animals do not respond to the positive feedback actions of estrogen by having LH surges, and hypothalamic NE turnovers do not increase during the afternoon as they do in normal rats. Female rats were given a single injection of testosterone propio-nate (50 µg s.c.) at 5 days of life and ovariectomized (OVX) at 100 days of age. Seven days later (day 0), estrogen capsules were inserted subcutaneously, and on day 2, their responses to NAL or morphine were examined. Comparable estrogen-treated gonadectomized controls also were studied. In control rats, NAL (10 mg/kg s.c.) markedly amplified the phasic secretion of plasma LH. In contrast, NAL had no effect on the basal afternoon secretion of LH in ASR. To determine if neonatal androgen treatment deleteriously affected opiate-tuberoinfundibular dopamine (TIDA)-serotonergic interactions, a second series of studies was performed. Estrogen-treated adult gonadectomized males, females and ASR were injected with morphine sulfate (10 mg/kg s.c). Blood was sequentially collected, thereafter, every 10 min for 70 min. Morphine produced a rapid rise in plasma PRL beginning within 10 min and peaking approximately 40 min after drug treatment. All 3 groups of rats secreted equivalent amounts of PRL, and no significant differences among the 3 groups were detected. We conclude that the failure of NAL to affect LH secretion in ASR is due to the permanent damage produced in the noradrenergic system by neonatal androgen treatment. The present data also demonstrate that prepubertal androgen treatment does not affect the ability of morphine to induce the release of PRL, an event thought to be mediated via interactions between the opiate, TIDA and serotonergic systems