Six patients with Cushing's disease received ketoconazole for 7-10 weeks following ketoconazole challenge test. Clinical and hormonal alterations in circulating cortisol, 17 OH progesterone, androstenedione and testosterone were assessed during the therapy. There was significant clinical improvement which corresponded to a fall in cortisol, androstenedione and testosterone. The rise in 17 OH progesterone and the fall in cortisol suggest a blockade at 17,20 desmolase and 11 B-hydroxylase in the cortisol bio-synthetic pathway.