A 19-year-old male patient with Cushing's disease was treated for 15 months with a gastric-insoluble preparation of o,p'-DDD. The daily o,p'-DDD dose (range, 2 to 12 g) was adjusted periodically according to the urinary excretion of 11-hydroxycorticosteroids. Because of a rise in the plasma ACTH level from 135 to 300 pg/ml 12 months after the start of the o,p'-DDD therapy, the dose was reduced from 6 to 2 g/day and external pituitary irradiation (4,480 rads) was initiated. Insulin-induced hypoglycemia and stimulation tests with luteinizing-hormone-releasing factor and thyrotropin-releasing hormone, performed before initiation of o,p'-DDD and six months after pituitary irradiation, did not reveal any disturbance in the secretion of human growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone or prolactin. The clinical and laboratory signs of Cushing's disease disappeared gradually, and the patient tolerated the drug well, even at a dose of 12 g/day. The only abnormalities found during o,p'-DDD treatment were low serum thyroxine levels, which returned to normal after discontinuation of the drug, and a transient drop in thrombocyte count. At present, two years after the discontinuation of o,p'-DDD therapy and pituitary irradiation, the patient is symptom free and receives no medication.