The capacity of the anterior pituitary to secrete prolactin (PRL) and gonadotropins was evaluated by TRH and GnRH stimulation, followed by metoclopramide (MC) administration 1 hour later, before and after clomiphene citrate (CC) priming in 8 endometriosis patients receiving GnRH agonist analog (Buserelin) therapy for 6 months. GnRH-analog treatment lowered the maximal PRL responses to TRH and MC stimulation in the luteal phase, compared to those of 8 normally menstruating control patients. The LH response to GnRH stimulation was also diminished, indicating pituitary desensitization, while the FSH response remained unchanged. Antiestrogen administration during GnRH-analog treatment further reduced the capacity of pituitary lactotropes to secrete PRL in TRH and MC tests, and it increased the LH response but not the FSH response to GnRH stimulation. These data suggest that CC affects the mechanisms controlling PRL and gonadotropin secretions in hypoestrogenic women after prolonged GnRH agonist analog treatment by different modes of action, the action on gonadotropes being stimulatory and that on lactotropes inhibitory.