To clarify the influence of estrogens on the metabolism of gonadotropin-releasing hormone (GnRH), we studied the metabolic clearance rate (MCR) of GnRH (MCRgnrh), and the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone (total and free fraction) in 9 sexually mature men and 7 women under basal conditions and after treatment with the antiestrogen tamoxifen (2 × 10 mg/day p.o.) for 7 days. In women, the medication was started on day 7 ± 1 of their menstrual cycles. To calculate the MCR, synthetic GnRH was continuously infused (1.53 µg/min) and its serum levels were measured by a radioimmunoassay. During tamoxifen treatment we observed a small but significant decrease in the MCR in men (455 ± 48 to 357 ± 46 ml/min/1.86 m<sup>2</sup>), whereas the known cyclic increase in the MCR in women was blunted (1,769 ± 147 to 1,558 ± 119 ml/min/1.86 m<sup>2</sup>). There was a small but significant increase in LH levels in women (8.3 ± 2.1 to 11.5 ± 2.5 mU/ml). LH and testosterone levels in men, and FSH and estradiol levels in both sexes did not change significantly. Conclusion: (1) estrogens regulate the MCRg<sub>GnRH</sub> either directly or by changing gonadotropin levels, but the effect is only slight; (2) an enhanced metabolism of GnRH may contribute to the feedback of estrogens on the secretion of gonadotropins, and (3) the sex-specific difference of the MCR is presumably not caused by estrogens.