In several respects prolactin is unique among anterior pituitary hormones. The primary regulation of prolactin secretion is mediated through hypothalamic inhibition, and the diagnosis of hyperprolactinemia can be established without the use of stimulation or suppression tests. Documenting the presence of hyperprolactinemia is not difficult–the challenge is in identifying the cause of the hormone hypersecretion. With immunoradiometric assays falsely low levels of prolactin are occasionally seen in patients with macroadenomas and very high serum prolactin (the hook effect). Macroprolactin should be suspected when a patient with hyperprolactinemia does not present with typical clinical symptoms, and all hyperprolactinemic sera should be screened for macroprolactin. With prolactinomas, prolactin levels generally parallel tumor size. Prolactin secreting macroadenomas are typically associated with levels that exceed 250 μg/l and may exceed 1,000 μg/l. Large non-functioning adenomas also lead to hyperprolactinemia but levels virtually never exceed 94 μg/l. Acquired and isolated prolactin deficiency is rare.