The effects of loperamide, an opiate analogue of the piperidine class on pituitary hormone secretion were evaluated in eight patients with Addison's disease. In all patients loperamide administration (16 mg orally) induced a marked fall in plasma ACTH levels (P less than 0.01), without affecting GH, PRL and LH levels. Plasma ACTH concentration fell significantly from 854 +/- 167 pg/ml (mean +/- SEM) to 460 +/- 123 pg/ml at 60 min (P less than 0.01). The inhibition persisted throughout the whole test period, the nadir being reached at 300 min. Low dose naloxone infusion 180 min after loperamide administration caused plasma ACTH to rise from 181 +/- 61 pg/ml to 539 +/- 99 pg/ml (P less than 0.01). The present data suggest that the opiate analogue loperamide is a potent inhibitor of ACTH secretion in patients with Addison's disease, which may be acting on mu receptors, since its effect is blocked by low doses of naloxone.