The aim of our study was to evaluate the activity of opioid receptors involved in the regulation of prolactin secretion in different kinds of hyperprolactinemic states (puerperal, idiopathic and tumoral subjects). Prolactin plasma level changes were measured after the acute administration of a met-enkephalin synthetic analogue. FK 33-824, and placebo. The prolactin-releasing effect of this drug, evident in control subjects, was blunted in patients affected by idiopathic hyperprolactinemia, and absent in puerperal and tumoral patients. These results indicate that hyperprolactinemia affects the activity of central opioid receptors, with the most evident effects in patients with highest prolactin plasma levels.