Trans-sphenoidal intrasellar implantation of radioactive rods was employed to treat Cushing's disease in our Institution between 1958 and 1981. The patients were followed at regular intervals after the procedure. The aim of this work is to assess retrospectively the results, comparing the short- (1 year) and long-term (average 21.8 years) effects of this treatment. Seventy-six patients received pituitary implantation of 90Y- and one of 198Au-labelled rods, delivering a dose of 100-150,000 rad. Complete remission was obtained in a few weeks to months in 57/76 patients (5 of whom required a second implantation); 2 patients died of meningoencephalitis and 3 of cardiovascular complications associated with hypercortisolism 1 to 2 months after surgery. In 12 patients bilateral adrenalectomy or external pituitary irradiation were required to achieve remission; one of them developed Nelson's syndrome 15 years after implantation. Two were lost at follow-up. Long-term follow-up was possible in 41 patients of the initial series. Of these, 40 were cured of the disease, with hypoadrenalism developing in 25, while recurrence was observed only in the patient treated with 198Au. The incidence of hypothyroidism was 50%, and that of hypogonadism 54%. Permanent diabetes insipidus developed in 1 subject. GH deficiency resulting in retarded growth was found in the youngest patient, who had been operated at the age of 14. In conclusion, interstitial irradiation of pituitary adenomas was a safe and effective procedure for the treatment of Cushing's disease.