Hypothalamic dopaminergic pathways are involved in the regulation of growth hormone and prolactin release from the anterior pituitary. Neuroendocrine studies in patients with multiple system atrophy (MSA), in whom there is a reported loss of hypothalamic dopamine, are few and contradictory. We therefore studied the neuroendocrine responses to 250 mg levodopa (plus 25 mg carbidopa) in subjects with MSA (n = 15), and compared them with age- and sex-matched healthy control subjects (n = 8). There were no significant differences in basal or post-levodopa levels of growth hormone (GH), growth hormone-releasing hormone (GHRH), glucose, insulin-like growth factor (IGF-1), or thyroid-stimulating hormone (TSH) between the groups. In patients with MSA, basal levels of prolactin were elevated (21.1 +/- 5.2 ng/mL [mean +/-standard error]) compared with control subjects (12.1 +/- 1.7, p <0.05), and after L-dopa there was increased variability in prolactin response with less suppression compared with control subjects. In conclusion, in patients with MSA, the GHRH and GH responses to L-dopa were preserved and were similar to responses in age-matched control subjects. In contrast, there was impaired dopaminergic suppression of prolactin secretion. In patients with MSA this may represent a selective dysfunction, rather than generalized loss, of tubero-infundibular dopaminergic neurones.