Hypercortisolism induces a functional suppression of the hypothalamus-pituitary-adrenal axis which is expected to subside within a year following either the removal of the cortisol producing adrenal adenoma or the withdrawal of glucocorticoid therapy. We report 3 women (35, 40 and 43 years old) with Cushing's syndrome due to cortisol producing adrenal adenoma. All had typical clinical and biochemical features of the syndrome dating from up to 4 years before surgery. Cortisol supplementation was given during the postoperative period (20 mg/day po at 9 AM, reduced to 10 mg/day after 6 months). Cortisol was withdrawn 16, 20 and 39 months after surgery, when 9 AM plasma concentration raised over 10 ug/dl [corrected]. An ACTH stimulatory test was performed until a normal response was obtained. Patients showed and abnormal response up to 16, 17 and 30 months after surgery, respectively. Complete recovery took place at 21, 36, and 55 months after the operation. We concluded that risk of hypocortisolism may persist up to 30 months after surgery for cortisol producing adenomas, due to complete or partial suppression of the hypothalamus-pituitary-adrenal axis.