Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal-weight and eight obese women received on two occasions a 3-h i.v. infusion of saline or hydrocortisone (HC) (1.5 mg.kg^-1.mn^-1). Plasma cortisol, insulin and glucose levels were measured every 30 min from time_-30 to time₂₄₀. Free fatty acids, adiponectin and PAI-1 levels were measured at time_-30, time₁₈₀ and time₂₄₀. At time₂₄₀, subjects underwent an insulin tolerance test to obtain an index of insulin sensitivity (K_ITT). Mean_30-240 cortisol level was similar in control and obese women after saline (74±16 vs 75±20 mg/l) and HC (235±17 vs 245±47 mg/l). The effect of HC on mean_180-240 insulin, mean_180-240 HOMA-IR and K_ITT was significant in obese (11.4±2.0 vs 8.2±1.3 mU/l, p<0.05; 2.37±0.5 vs 1.64±0.3, p<0.05; 2.81±0.9 vs 3.32±1.02%/mn, p<0.05) but not in control women (3.9±0.6 vs 2.8±0.5 mU/l; 0.78±0.1 vs 0.49±0.1; 4.36±1.1 vs 4.37±1.2 %/min). In the whole population, the quantity of visceral fat, estimated by CT-scan, was correlated with the increment of plasma insulin and HOMA-IR during HC infusion [mean_30-240 insulin (r=0.61, p<0.05), mean_30-240 HOMA-IR (r=0.66, p<0.01)]. PAI-1 increase between time₁₈₀ and time₂₄₀ after HC was higher in obese women (+25%) than in controls (+12%) (p<0.05), whereas no differential effect between groups was observed for free fatty acids or adiponectin. A moderate hypercortisolism, equivalent to that induced by a mild stress, has more pronounced consequences on insulin sensitivity in abdominally obese women than in controls. These deleterious effects are correlated with the amount of visceral fat.