Recent studies indicate that experimentally induced hyperinsulinemia may reduce serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S). Serum DHEA and DHEA-S decrease in diabetic patients, but the mechanism by which hyperglycemia decreases DHEA and DHEA-S is unknown. In this study, we investigated the effect of hyperglycemia on DHEA and DHEA-S in impaired glucose tolerance (IGT) by means of the 75g-oral glucose tolerance test (OGTT). We selected 30 male IGT patients receiving diet therapy only, whose insulinogenic Index was under 0.3. Oral glucose challenge significantly reduced DHEA (P = 0.0001) and DHEA-S (P < 0.05) at 60 and 120 min after OGTT. Setting the value of DHEA and DHEA-S at time zero as 100%, we calculated the DHEA and DHEA-S values at 60 and 120 min after OGTT as %DHEA(-S) 60 min and %DHEA(-S) 120 min, respectively. DHEA and DHEA-S at time zero showed no correlation with BMI, HbA1c, the sum of insulin values (sigma IRI) or the area under the curve of plasma glucose (AUC). We found decreases in %DHEA 60 min (r = -0.411, P < 0.05), %DHEA-S 60 min (r = -0.508, P < 0.01) and %DHEA-S 120 min (r = -0.393, P < 0.05) as AUC increased, but sigma IRI showed no correlation with %DHEA(-S) 60 min or %DHEA(-S)120 min. We conclude that the depression of DHEA and DHEA-S after OGTT is attributable to hyperglycemia in male Japanese IGT with low insulin response.