SUMMARYThe effects ofl‐DOPA administration on hypothalamic‐pituitary‐adrenal function were studied in five normal subjects and in five patients with active acromegaly. In acromegalic patients, orall‐DOPA (500 mg every 4 h for six doses) failed to alter the urinary excretion of 17‐hydroxycorticoids (17‐OHCS), 17‐oxosteroids (17‐OS), and tetrahydro‐11‐desoxycortisol (tetrahydro‐comp S). However, when cortisol synthesis was blocked with oral metyrapone, enhancement of excretion of 17‐OHCS, 17‐OS, and tetrahydro‐comp S byl‐DOPA became apparent in acromegalic patients but not in the normals. In patients with acromegaly, on the day of metyrapone administration, the mean excretion rates of 17‐OHCS, 17‐OS, and of tetrahydro‐comp S were 8.6 mg, 6.4 mg and 4.1 mg/24 h, respectively. When 500 mgl‐DOPA was co‐administered with metyrapone, the corresponding values increased significantly (P<0.01) to 14.9 mg, 9.0 mg and 7.7 mg/24 h. This effect ofl‐DOPA was not observed in the normal subjects. It was concluded thatl‐DOPA markedly enhanced the hypothalamic‐pituitary‐adrenal response to metyrapone in acromegalic patients, but not in normal subjects.l‐DOPA (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of ACTH. The unusual pituitary‐adrenal response tol‐DOPA in acromegaly may reflect: (1) a supersensitive reaction of the pituitary‐adrenal axis tol‐DOPA; (2) a paradoxical response of the pituitary‐adrenal a