© 2016 Informa UK Limited, trading as Taylor & Francis Group. Aims: To test the hypothesis that macroprolactinemia is an extra-pituitary phenomenon by showing that the pituitary production of prolactin in patients with hyperprolactinemia due to macroprolactin is comparable to that in normoprolactinemic women and different from that in women with monomeric hyperprolactinemia. Methods: Twenty-five women were studied: eight with macroprolactin hyperprolactinemia, eight with monomeric hyperprolactinemia, and nine controls. Prolactin levels were measured before and after precipitation with polyethylene glycol at baseline and at 5, 10,15, 30, and 60 min after metoclopramide administration (10 mg i.v.) in the three groups. Results: The response profile of total and monomeric prolactin following the administration of metoclopramide was similar in women with monomeric hyperprolactinemia and normoprolactinemia but different in women with macroprolactinemia. The areas under the curve for total and monomeric prolactin were higher in patients with macroprolactinemia than in the other two groups (p < 0·0001). The maximal concentration of monomeric prolactin was reached before that of total prolactin in macroprolactinemic patients but the differences were not significant. Discussion: Our findings support the hypothesis that prolactin secretion is comparable in women with macroprolactinemia and in normoprolactinemic women. The dynamics of the secretion suggest that the formation of prolactin complexes is an extra-pituitary process.