Five patients with pituitary dependent Cushing's syndrome and two with adrenal carcinoma were treated with increasing doses of trilostane (up to 1440 mg daily). There was no consistent fall in serum cortisol levels. In addition there was no rise in the levels of precursors immediately preceding the proposed site of action of trilostane. These results suggest that trilostane does not effectively block the enzyme 3 beta-hydroxysteroid dehydrogenase delta 4,delta 5 isomerase in patients with Cushing's syndrome and that it should no longer be recommended for their treatment.