Fifty-nine patients with Cushing's syndrome, due to adrenocortical tumor, were studied and treated during the period 1953 through 1983 at Vanderbilt University Medical Center. Cushing's syndrome is caused by hypercortisolism that can be due to (1) medicinal use of steroids, (2) excess pituitary secretion of adrenocorticotropin (ACTH) (Cushing's disease), (3) adrenocortical tumor, benign or malignant, and (4) the ectopic ACTH syndrome. Clinical and endocrinologic features of Cushing's syndrome are described, and differential diagnosis of adrenocortical tumor by precise endocrinologic studies is detailed. Computerized axial tomographic (CAT) scan is currently the most accurate imaging modality for preoperative localization of tumors. Preoperative differential diagnosis between adrenocortical adenoma and carcinoma has become fairly accurate. Operative approaches in each category are described. Follow-up from 1 to 30 years has been completed for all patients, except for one who was lost after 7 years. Results of surgical treatment of adrenocortical adenomas are excellent, but the salvage from adrenocortical carcinomas is poor.