To date, data on pituitary adenomas in MEN type 1 (MEN1) still have to be evaluated. We analyzed the data of a large series of 324 MEN1 patients from a French and Belgian multicenter study. Data on pituitary disease were compared with those from 110 non-MEN1 patients with pituitary adenomas, matched for age, year of diagnosis, and follow-up period. Genetic analysis of the MEN1 gene was performed in 197 of the MEN1 patients. In our MEN1 series, pituitary disease occurred in 136 of 324 (42%), less frequently than hyperparathyroidism (95%, P < 0.001) and endocrine enteropancreatic tumors (54%, P < 0.01). Mean age of onset of pituitary tumors was 38.0+/-15.3 yr (range, 12-83 yr). Pituitary disease was associated with hyperparathyroidism in 90% of cases, with enteropancreatic tumors in 47%, with adrenal tumors in 16%, and with thoracic neuroendocrine tumors in 4%. Pituitary disease was the initial lesion of MEN1 in 17% of all MEN1 patients. MEN1 pituitary adenomas were significantly more frequent in women than in men (50% vs. 31%, P < 0.001). Among the 136 pituitary adenomas, there were 85 prolactinomas and 12 GH-secreting, 6 ACTH-secreting, 13 cosecreting, and 20 nonsecreting tumors. Eighty-five percent of MEN1-related pituitary lesions were macroadenomas (vs. 42% in non-MEN1 patients, P < 0.001), including 32% of invasive cases. Among secreting adenomas, hormonal hypersecretion was normalized, after treatment, in only 42% (vs. 90% in non-MEN1 patients, P < 0.001), with a median follow-up of 11.4 yr. No correlation was found between the type of MEN1 germ-line mutation and the presence or absence of pituitary adenoma. Our study, based on a large group of MEN1 patients, shows that pituitary adenomas occur in 42% of the cases and are characterized by a larger size and a more aggressive presentation than without MEN1.