D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824) is a stable long acting analog of methionine-enkephalin. FK 33-824 (0.5 or 1.0 mg), elicited plasma GH and PRL responses in normal subjects. In 23 patients with pituitary dwarfism, the response of plasma GH was markedly impaired, while PRL responded to a variable degree. In patients with acromegaly, there was little or no increase in GH and PRL after FK 33-824. Plasma GH increased to a variable degree after FK 33-824 in patients with hyperprolactinemia, with little change in plasma PRL. FK 33-824 decreased plasma cortisol in normal subjects and patients with pituitary disease. These results show that patients with acromegaly and hyperprolactinemia due to pituitary adenomas and patients with pituitary dwarfism do not respond well to FK 33-824, presumably because of hypothalamic or pituitary derangement.