The causes of glioma, the most common type of primary malignant brain tumor, are poorly understood. This study compared the personal and first-degree familial medical histories of 462 adults newly diagnosed with glioma in the San Francisco Bay Area between August 1, 1991, and March 31, 1994, with those of 443 controls who were frequency-matched on age, sex, and ethnicity. Cases and controls had equivalent personal histories of cancers other than brain cancer and most nervous system conditions, but they differed significantly regarding histories of epilepsy, seizures, or convulsions 3 or more years prior to diagnosis (odds ratio = 3.3, 95% confidence interval (CI) 1.4-7.9), chickenpox (odds ratio = 0.4, 95% CI 0.3-0.6), and shingles (odds ratio = 0.5, 95% CI 0.3-0.8). Four cases (less than 1%) and no controls had known genetic disorders (three had neurofibromatosis and one had tuberous sclerosis). Cases and controls had similar family histories of cancer and seizures. However, the odds ratio for a validated family history of primary brain tumor was 2.3 (95% CI 1.0-5.8). These results suggest that although family history of any cancer probably is not an important risk factor for adult glioma, a family history of brain tumors may play a role. Variation in exposure to or biologic response to common viral infections might play a greater role in the etiology of adult glioma than family history.