Testing with ovine corticotropin-releasing hormone (CRH) has facilitated the differential diagnosis of Cushing syndrome, which is often not straightforward. We provide our experience between January 1989 and August 1993 with 30 patients with Cushing syndrome and describe 4 cases in detail to illustrate how CRH testing can be successfully applied to some of the difficulties encountered in the evaluation. CRH testing proved to be particularly useful in distinguishing cases of Cushing syndrome of adrenal etiology from those of Cushing disease with low or undetectable adrenocorticotropin (ACTH) levels. CRH testing during petrosal sinus sampling was also found to help distinguish the ectopic ACTH syndrome from pituitary-dependent Cushing syndrome. Our cases illustrate the need for careful biochemical evaluation before proceeding to imaging studies. Using CRH testing to evaluate cases of Cushing syndrome in which standard testing was inconclusive can provide useful information and lead to a more rapid determination of etiology and definitive therapy than previously possible.