Autonomous secretion of prolactin (PRL) by a pituitary prolactinoma is a relatively common endocrine disorder characterized by increased serum concentrations of PRL and symptoms of menstrual irregularity, infertility, and galactorrhea in women and impotence and lack of libido in men (1). These clinical symptoms are common, and measurement of serum PRL is a key investigation used to identify the minority of patients who have hyperprolactinemia and warrant further investigation and who may benefit from treatment with dopamine agonists. Unfortunately, the laboratory finding of hyperprolactinemia is not specific because increased serum immunoreactive PRL may be caused by the presence of a high-molecular-mass complex of PRL (macroprolactin), which has been found in asymptomatic patients (2) and therefore appears to lack the biological activity associated with the normal, monomeric 23-kDa form of PRL. This problem is compounded by the limited sensitivity and specificity of pituitary imaging techniques in the confirmation of prolactinoma (1). The report by Suliman et al. (3) in this issue carries two messages of considerable importance for clinical chemists: (a) hyperprolactinemia attributable to macroprolactin is a frequent cause of misdiagnosis and mismanagement of patients; and (b) this problem could be avoided if laboratories applied a screening test to all samples with increased total serum PRL to detect the presence of macroprolactin and reported a measure of the bioactive, monomeric PRL concentration. Using gel-filtration chromatography (GFC), Suh and Frantz (4) demonstrated nearly 30 years ago that minor proportions of the total serum immunoreactive PRL circulate as high-molecular-mass forms, which are referred to as big PRL (40–60 kDa) and big-big or macroprolactin (150–170 kDa). Hyperprolactinemia attributable to a predominance of the fraction with the highest molecular mass was observed by Andersen et al. (5) in a patient complaining of infertility who subsequently conceived spontaneously. Andersen et al. (5) demonstrated the bioactivity …