The effect of human chorionic gonadotropin (hCG) administration on the pituitary and luteal responses to acute gonadotropin-releasing hormone (GnRH) administration at the mid luteal phase (LP) were studied in 20 infertile women. Patients were divided into 2 groups. In 1 group (n = 8), hCG (5,000 IU i.m.) was injected in a single shot on day 5 of LP. Sixty hours later (day 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 with GnRH was performed on day 8 of an untreated LP. Plasma LH, FSH, β-hCG, progesterone and estradiol (E<sub>2</sub>) were assayed. The responsiveness of different hormones to GnRH was evaluated as integrated secretory area for 120 min after injection (sISA) and as the absolute increase with respect to the area under basal conditions before a GnRH administration (bISA). hCG-treated patients showed higher basal and bISA plasma values of LH/hCG than controls (p < 0.01). After GnRH the amplitude of LH secretion was similar in both groups. Also bISA and sISA values of FSH were similar in both groups. Basal and bISA plasma values of progesterone and E<sub>2</sub> secretion were similar in hCG-treated and control patients. After GnRH administration a significant increase in progesterone (p < 0.01) and E<sub>2</sub> (p < 0.05) secretion was seen in controls, while this response failed in hCG-treated patients, so that the amplitude of progesterone secretion was significantly greater in controls than in hCG-treated patients (p < 0.01). The results of this study suggest that hCG administration leads to a dissociation of corpus luteum secretion from hypothalamic-pituitary axis, probably due to a transitory exhaustion of corpus luteum steroidogenesis in respect to endogenous gonadotropin stimuli.