The pituitary and corpus luteum responses to acute gonadotropin-releasing hormone (GnRH) administration at the mid-luteal phase (LP) were studied in 24 infertile women. Patients were randomly divided into two groups. In one group (n = 12) metoclopramide (MCP, 10 mg orally 3 times daily) was administered from day 0 or 1 of the LP for 7 days. On day 7 or 8 of LP blood samples were taken every 15 min for 180 min; then 25 µg GnRH were acutely administered intravenously and blood samples taken at 185, 195, 210, 225, 240, 255, 270, 285 and 300 min. In the other 12 patients the same experimental design was performed on day 7 or 8 of an untreated LP. Plasma prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estradiol (E<sub>2</sub>) were assayed. The responsiveness of the different hormones to GnRH was evaluated as the integrated secretory area for 120 min after injection (sISA = stimulated integrated secretory area) and as the percentage increase (ΔA) with respect to the area under basal conditions before GnRH administration (bISA = basal integrated secretory area). MCP-treated women showed higher basal PRL levels (p < 0.01) and lower basal plasma concentrations and bISA (p < 0.01) values of LH than controls. After GnRH a more marked response of LH secretion was observed in the treated group (p < 0.01), so that the absolute values of sISA were superimposable in both groups. Basal and stimulated FSH secretion did not differ significantly in the study groups. Basal plasma and bISA values of progesterone were also decreased in MCP-treated subjects. After GnRH injection the absolute values of progesterone sISA were greater in controls (p < 0.01), but ΔA values were similar in both groups. Basal and stimulated E<sub>2</sub> secretion was also superimposable in both groups. In conclusion, mild MCP-induced hyperprolactinemia during LP affects the hypothalamic-pituitary axis by a derangement of gonadotropin secretion which in turn determines a blunted functional activity of the corpus luteum.