It has been previously reported that GnRH is capable of inducing a PRL response in intact and castrated men treated with estradiol benzoate for 8-9 days. To further support the hypothesis of an estrogen-dependence of the PRL response to GnRH, GnRH was administered, either as a bolus or as a continuous infusion, to 45 normal women during various phases of their menstrual cycles. Synthetic GnRH (100 micrograms intravenous bolus) elicited a significant increase (mean 175%) in circulating PRL levels in nine women studied during the periovulatory phase of the menstrual cycle (days 14-17). Similarly, GnRH infusion (0.2 micrograms/min X 3 h) induced a PRL response (mean 148%) in six women studied during the same period. In contrast, saline infusion induced a modest decrease (37%) in plasma PRL levels in five women studied during the periovulatory period. No significant changes in circulating PRL levels were found after GnRH administration as a bolus or a continuous infusion, in 13 women during the late follicular phase (days 10-13) and in 12 women during the midluteal phase (days 21-24). Synthetic GnRH elicited the expected increase in gonadotropin levels during all phases of the cycle studied. The maximal response was found for both LH and FSH during the periovulatory phase of the cycle. In conclusion, the data confirm that GnRH is capable of stimulating a PRL response in humans and again suggest that this response is estrogen-dependent. Finally, a temporal correlation between the midcycle gonadotropin peak and the positive PRL response to exogenous GnRH has been established.