A 58-yr-old man presented a Cushing's syndrome gradually developed for two years, and a cervical tumor. Urinary free cortisol and 17-hydroxy-corticosteroids were elevated and non suppressible under high dose dexamethasone (8 mg a day X 2 days). Plasma calcitonin (7,200 pg/ml), CEA (803 ng/l), beta LPH (624 pg/ml), and CRF (29 pg/ml) were elevated. Total thyroidectomy revealed a medullary carcinoma of the thyroid. Postoperatively the Cushing's syndrome disappeared and plasma CRF became undetectable although plasma calcitonin remained elevated. One out of 3 CRF antisera tested for immunocytology was positive in 10 to 30% of the cells. In tumor extract, CRF (RIA) concentration was 4.75 ng/g. There was no detectable ACTH in the tumor by biochemical as well as immunocytochemical method. In the present report, the next evidences are--for the first time--simultaneously present to demonstrate an ectopic secretion of CRF by a medullary thyroid carcinoma: presence of CRF in systemic blood being undetectable after surgery; cure of the clinical and biological features of Cushing's syndrome after thyroidectomy; characterization of CRF immunoreactivity in tumor. Taken together, the radioimmunological and the immunocytochemical data suggest the production of several molecular forms of CRF.