It has been previously shown that in normal women during the periovulatory period, prolactin (PRL) levels increase after the administration of nonspecific stimuli, such as growth hormone-releasing hormone or gonadotropin-releasing hormone (GnRH). In order to gain insight into the mechanism of this response, we have tested the effect of a naloxone infusion (1.6 mg/h) on the PRL response to GnRH in 5 normal females, aged 20–27 years, tested during the periovulatory period. Naloxone was administered starting 60 min before GnRH administration (100 µg as an i.v. bolus). Naloxone clearly blunted the PRL response (basal 10.7 ± 1.7 ng/ml, peak 11.8 ± 0.2 ng/ml at 30 min, versus: basal 9.0 ± 0.5 ng/ml, peak 20.6 ± 3.9 ng/ml at 45 min after GnRH alone; significance of difference between peaks: p < 0.05). A secondary late increase of PRL levels was observed, reaching about 60% of basal levels at 120 min (16.8 ± 2.6 ng/ml). These data indicate that periovulatory PRL dynamics are altered by naloxone administration and suggest a possible involvement of opioid peptides in the ‘paradoxical’ PRL response to GnRH in norm