CRH-stimulation-test with 100 micrograms ovine or human corticotropin releasing hormone is useful in making the differential diagnosis of established Cushing's syndrome (N = 45). Only in 3 patients we did not find the expected result. In one patient with proven pituitary ACTH-dependent Cushing's disease there was no ACTH- and cortisol-increase after CRH-stimulation, whereas in two patients with ectopic ACTH-production due to a lung tumour there was a significant ACTH-increase after CRH-stimulation. The CRH-test was repeated 7-10 days after transsphenoidal surgery in 30 patients with Cushing's disease. Successfully operated patients exhibit no, blunted or normal ACTH responses to CRH. In patients with autonomous adrenal cortisol secretion after surgery the ACTH response to CRH can already be demonstrated when cortisol levels are still undetectable. The same could be shown for patients after long-term corticoid therapy suggesting that the cause of adrenal failure after unilateral adrenalectomy for Cushing's syndrome or long-term corticoid therapy is due to hypothalamic CRH deficiency. Acute administration of corticoids suppressed CRH-induced ACTH-secretion in normals and patients with pituitary ACTH-dependent Cushing's disease suggesting the pituitary level as target side for the acute feedback inhibition. Our results with different stimuli of the ACTH-secretion in normal controls (N = 6) with and without intravenous dexamethasone administration indicate a multihormonal control of pituitary adrenal activity.--Measurements of CRH-levels with a homologous human CRH-radioimmunoassay in patients with pituitary ACTH-dependent Cushing's disease did not help in differentiating these patients according to their possible pathophysiology (functional hypothalamic or autonomous pituitary cause of ACTH-hypersecretion).(ABSTRACT TRUNCATED AT 250 WORDS)