Human adipocytes from patients with chronic endogenous hypercortisolism (Cushing's syndrome) showed a statistically significant decrease in insulin binding at low unlabelled-insulin concentrations but no change in receptor numbers (Cushing's 180,000 +/- 48,000 (3) receptors/cell and controls 189,000 +/- 30,000 (7)) together with a fourfold decrease in apparent receptor affinity (ED50: Cushing's 2.25 x 10(-9) M and controls 0.57 x 10(-9) M) and a decreased sensitivity to the antilipolytic effect of insulin. These events could represent the final situation of a chronic and endogenous regulation by high levels of cortisol of insulin receptors in human adipose tissue.