Ketoconazole has been successfully used in short-term treatment of Cushing's syndrome. We treated 4 patients who had Cushing's disease with ketoconazole administered during 5 to 18 months. Two of them are still controlled after 15 months of treatment and 7 months after treatment was withdrawn. In the other two patients, treatment was ineffective primarily and after 5 months. Our data confirm the usefulness of ketoconazole in the treatment of Cushing's disease, but they also show that primary resistance and tachyphylaxis in long-term treatment may occur, as previously reported.