The aim of this study was to ascertain whether there is a correlation between gonadal steroids and opioid control of prolactin (PRL) secretion. Four castrated men, aged 18 to 24 years were submitted to intravenous injection of 250 ug of a met-enkephalin analog (D-Ala2-Mephe4-Met-(o)-ol-Enkephalin, FK 33824) (DAMME). In normal men DAMME injection was also performed on the 6th day after treatment with clomiphene citrate (CC) (200 mg/day for 5 days), a specific nonsteroidal estrogen receptor blocker. In castrated men and in normal men after CC treatment, there was a lower PRL response to DAMME than in controls (P less than 0.0005). These results suggest that gonadal steroid deficiency seems to cause a change in the opioid system and/or dopaminergic control of prolactin secretion.