To gain insight into the PRL-releasing effect of GnRH, serum PRL and gonadotropin responses to a 10-microgram iv bolus dose of exogenous GnRH were studied in hypergonadotropic hypogonadal women (HHW) and patients with functional hypothalamic amenorrhea (FHA). The results were compared with those obtained in normal cycling women during the early follicular phase of the cycle. GnRH induced a significant increase in PRL levels (P less than 0.001) in HHW compared to early follicular phase women, in whom no significant response occurred. In HHW, the maximal PRL percent increment was positively correlated with the ratio of the maximal percent increments of FSH and LH (r = 0.93). GnRH induced a significant increase in PRL levels in every FHA patient, but in four of them (high PRL responders), the PRL response was at least 5-fold greater than in the other six (low PRL responders). The clinical profiles, basal hormone concentrations, and LH responses to GnRH were similar in these two groups of FHA patients, but the FSH response to GnRH was greater (P less than 0.05) in the high PRL responders. The maximal percent increment of PRL was also positively correlated with the maximal percent increment of FSH (r = 0.76; P = 0.01). These data demonstrate that in these two hypogonadal models, the PRL response to exogenous GnRH corresponds to the FSH response and suggests that GnRH-stimulated PRL release may be mediated by a paracrine effect between FSH-enriched gonadotrophs and lactotrophs.