Objective: Serum PRL levels at presentation may be useful in distinguishing between disconnection hyperprolactinemia in non-secretory pituitary adenomas and prolactinomas in order to guide appropriate therapy; however, there is a debate regarding the discriminatory PRL thresholds. We aimed to examine PRL concentrations at presentation in a cohort of histologically proven non-functioning pituitary adenomas (NFPA). Design and methods: Retrospective case note analysis was performed. Clinical, biochemical, histopathological and radiological data were recorded and analyzed. Complete data were available for 250 subjects with NFPA. Results: Of the study population, 44.8% were hyperprolactinemic at presentation, 55.3% of whom were female. Of those with hyperprolactinemia, 73.2% had PRL<1000 mIU/l on presentation, 24.1% had PRL between 1000 and 1999 mIU/l. Only 2.7% (no.=3 females, 1.2% whole cohort) had PRL>2000 mIU/l (94.3 ng/ml), 2 of whom were pregnant. No male subject and no subjects with an intrasellar macroadenoma had serum PRL>1000 mIU/l (47.2 ng/ml). Overall, serum PRL was not higher among 43 subjects taking medications known to raise PRL. Conclusions: Our data support recent evidence that the serum PRL concentration is rarely >1000 mIU/l in males, or >2000 mIU/l in females, with non-functioning macroadenomas and that, once other contributing factors to the hyperprolactinemia have been excluded, a trial of dopamine agonist therapy for such lesions is indicated.