Previously we observed that prolactin (PRL) is secreted in response to gonadotropin-releasing hormone (GnRH) in normal women during the periovulatory phase of the menstrual cycle. Because sedative drugs affect the neurotransmitters involved in the regulation of PRL secretion, we investigated PRL responsiveness to GnRH in pre- and postmenopausal female subjects during prolonged treatment with benzodiazepines (six-60 months). In both pre-and postmenopausal patients who were not on benzodiazepine treatment, GnRH infusion (0.2 micrograms/min for 3 hr) was ineffective in eliciting a PRL response. In six premenopausal women treated with benzodiazepines, basal PRL concentrations were not influenced by the drug in four subjects (range 4.0-15.7 ng/ml) and were slightly elevated in two subjects (23 and 30 ng/ml). In six treated postmenopausal women, basal PRL concentrations were in the normal range (7.5-11.0 ng/ml). GnRH infusion induced a progressive increase in PRL concentrations which reached a peak at 120 min in the premenopausal subjects (mean % SEM increase: 64 +/- 30.5%) and at 60-90 min in the postmenopausal subjects (mean % increase: 110.6 +/- 34.7%). A saline infusion, performed on a separate day during benzodiazepine treatment as a control, did not influence PRL.