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 micrograms 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 less than 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 normal subjects.