To assess the therapeutic value of a dopaminergic drug on abnormal ACTH secretion, we studied the effect of bromocriptine during short and long-term treatment in nine patients with active pituitary-dependent Cushing's syndrome. The single oral dose effect of bromocriptine (2.5 mg at 0800 h) on ACTH samples obtained every half hour for 3 h, was studied in six patients with Cushing's disease; in no case was suppression of ACTH observed. In five patients, the effect of bromocriptine was also investigated after its administration for two consecutive days (5 mg/d) with plasma samples taken every half hour for 12 h; in three cases no suppression of plasma ACTH was observed, while the other two showed a significant decrease. Three of our patients (a nonresponder to the single dose, a responder to the two-day treatment, and an untested patient) were subjected to prolonged bromocriptine administration (2-45 months). In the first two patients only, biochemical data and clinical symptoms showed improvement, while the other patient showed only initial benefit. These data show that bromocriptine may occasionally reduce ACTH secretion in pituitary-dependent Cushing's syndrome, and that a single oral dose bromocriptine test fails to identify the patients who will benefit from this treatment.