OBJECT: Little is known about the epidemiology of meningioma, the most frequently reported primary brain tumor in the US. The authors undertook a case-control study to examine the relationship between family and personal medical history and meningioma risk. METHODS: The authors compared the personal and first-degree family histories of 1124 patients with meningioma (age range 20-79 years) in Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 Houston counties between May 1, 2006, and February 26, 2010, and the histories of 1000 control individuals who were frequency-matched for age, sex, and geography. RESULTS: The patients were more likely than the controls to report a first-degree family history of meningioma (OR 4.4, 95% CI 1.6-11.5), and there was an even stronger association in younger cases. The patients were less likely than controls to report immune conditions including allergy (OR 0.6, 95% CI 0.5-0.7) but were more likely to report a history of thyroid cancer (OR 4.7, 95% CI 1.02-21.5) or leukemia (OR 5.4, 95% CI 1.2-24.1) (most after radiotherapy). Among women, patients were more likely than controls to report hormonally related conditions--uterine fibroid tumors (OR 1.2, 95% CI 1.0-1.5), endometriosis (OR 1.5, 95% CI 1.5-2.1), and breast cancer (OR 1.4, 95% CI 0.8-2.3). CONCLUSIONS: The influence of genetics, the immune system, and radiation near the head on meningioma risk is suggested in the authors' findings; the role of hormones is intriguing but requires further study.