Of 206 patients with Cushing's syndrome observed from 1975 through 1991, 144 (69.9%) had pituitary.dependent Cushing's disease. Of the 110 patients who underwent pituitary surgery, 31 (28%) developed an early recurrence and 23 patients (20%) had a late relapse 1 to 5 years after primary pituitary exploration. We performed a one-or two-step total bilateral adrenalectomy in 43 patients---9 men and 34 (79.4%) women, with an average age of 47.5 years (range 13--58 years). Thirty-three of these patients had already been treated by previous transsphenoidal surgery or alternatively by external pituitary irradiation over a period of 1 to 10 years prior to adrenal surgery. Thirty-one patients underwent adrenalectomy by a double lumbar access or left lumbar and right subcostal incisions. In our series of 55 operations, perioperative complications included two splenectomies and two hemorrhages (7.3%). The early mortality rate was 3.6% (two patients). Minor complications consisted of wound infection (13.5%), bronchopneumonia or pneumothorax (four cases) with a 7-to 12-day longer hospital stay. Nelson syndrome occurred in 6 of 41 patients (!4.6%). We therefore believe that bilateral adrenalectomy does play a major role in the treatment of patients with pituitary-dependent Cushing's disease unsuccessfully managed by transsphenoidal surgery. It represents the definitive therapy for those patients in whom hypophysectomy was not able to provide satisfactory control of the disease.