Twenty-five patients were identified with non-pituitary, nonadrenal ACTH-secreting tumors (bronchial carcinoid, bronchial small cell carcinoma, pancreatic islet cell carcinoma, medullary thyroid carcinoma, thymic carcinoids, metastatic adenocarcinoma, and pancreatic cystadenoma). Clinical features were weakness, hypertension, cushingoid appearance, peripheral edema, personality disorders, and hyperpigmentation. Biochemical features were a markedly increased urinary free cortisol level (all patients), hypokalemia (71 percent of patients), and an elevated ACTH level (72 percent of patients). Surgical therapy consisted of bilateral total adrenalectomy (56 percent of patients). Twelve percent underwent transsphenoidal hypophysectomy and 36 percent had excision of their tumor. No surgical therapy was undertaken in 28 percent. Bilateral total adrenalectomy in patients with a slow-growing malignancy or an unknown tumor secreting ACTH is beneficial in relieving symptoms and prolonging life. Excision of nonmalignant ACTH-producing tumors yields an excellent long-term prognosis.