Chronic therapy of a patient with Nelson's syndrome for 2 years with 300 micrograms SMS 201-995 per day resulted in a significant decrease in circulating ACTH levels, normalization of the visual field defect and of loss of visual acuity of one eye, and stabilization of tumour growth, without radiological evidence of shrinkage of the pituitary tumour. In two other patients with Nelson's syndrome, SMS 201-995 acutely inhibited circulating ACTH levels. This effect could be shown best if cortisol replacement was temporarily withheld. SMS 201-995 did not affect plasma ACTH and cortisol levels in three patients with untreated Cushing's disease.