To determine whether the combined glucose-thyrotropin-releasing hormone (TRH) test can be a useful method for the evaluation of the hypothalamic somatostatinergic activity, we investigated whether TRH-induced thyroid stimulating hormone (TSH) secretion can be suppressed by the oral glucose administration that stimulates the hypothalamic somatostatin (SRIH) secretion. Six tests were performed in ten healthy young men. Test 1: 1 ml of normal saline was intravenously administered at 0 min. Test 2: TRH was administered intravenously at 0 min. Test 3: Glucose, 75 g, was administered orally at -60 min. Test 4: Glucose and TRH were administered as above. Test 5: Pyridostigmine (PST), 120 mg, was given orally at -90 min followed by the administration of GH and TRH as above. Basal TSH levels were suppressed slightly, but significantly. In Test 3 compared to those observed in Test 1. The oral glucose administration also significantly suppressed TRH-stimulated TSH response by 27-35% between 40 min and 80 min in Test 4. In contrast, the pretreatment with PST completely reverted the suppressive effect of glucose on TRH-stimulated TSH response in Test 5. These data suggest that the increased hypothalamic SRIH secretion induced by oral glucose administration can suppress TRH-stimulated TSH response in normal men, and the combined glucose-TRH test can be a useful method to evaluate the hypothalamic somatostatinergic activity.