We studied the dopaminergic control of lactotroph cells in the anterior pituitary of parkinsonian patients and age-matched normal subjects. The resting levels of prolactin and the TRH-induced rise in prolactin were normal in Parkinson disease. Levodopa elicited a normal suppression of prolactin concentrations in parkinsonian subjects; the major abnormality to emerge was attenuation of the response to thyrotropin-releasing hormone (TRH) in the parkinsonian patients following administration of Sinemet (levodopa plus carbidopa) or bromocriptine. These findings imply pathology of extrastriatal dopamine systems in Parkinson disease. Since the addition of carbidopa enhanced the suppression of prolactin induced by levodopa, exogenous levodopa probably acts predominantly through the formation of dopamine in the hypothalamus, but inside the blood-brain barrier, rather than as a direct effect of circulating dopamine on the anterior pituitary or areas of the hypothalamus outside the blood-brain barrier.