To test whether chronic thyroid hormone excess influences the hypothalamic-pituitary-testicular axis, 8 hyperthyroid men were given two identical intravenous GnRH tests. The first test was performed before any treatment had been instituted, the second 6–13 months later, when medical treatment had made the patients euthyroid. Although basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) levels were of similar magnitudes before and after the medical treatment, LH and FSH responsiveness to gonadotropin-releasing hormone (GnRH), as reflected by the hormone incremental areas (U/l × min), were significantly larger in the thyrotoxic state compared with the euthyroid state (LH incremental areas: 3,999 ± 665 vs. 2,640 ± 430, p < 0.02; FSH incremental areas: 825 ± 193 vs. 542 ± 98, p < 0.05). Furthermore, serum T increased significantly in response to GnRH when the patients were hyperthyroid (T incremental area: 162 ± 51 p < 0.02), but failed to do so when they were euthyroid (T incremental area: 92 ± 53, NS). These results imply that chronic thyroid hormone excess makes the pituitary gonadotrophs ‘hypersensitive’ to exogenous GnRH. This may in turn explain why human Ley dig cells respond more powerful to exogenous GnRH in thyrotoxic patients than in euthyroid subjects.