Pituitary gland tumors are usually benign but are associated with substantial morbidity. Their etiology is largely unknown. We conducted a population-based case-control study of potential risk factors for pituitary tumors in Southeast England. Information on medical and reproductive history, female sex hormones, and cigarette smoking was collected by personal interview from 299 cases and 630 controls aged 18 to 59 years. Tumor risk was reduced in subjects reporting a past diagnosis of hay fever [odds ratio (OR), 0.7; 95% confidence interval (CI), 0.5-1.0] but not asthma or eczema. Risk was raised in women who were postmenopausal 1 year before diagnosis (OR, 3.2; 95% CI, 1.6-6.2), especially if menopause was surgically induced (OR, 6.7; 95% CI, 2.2-19.9) or occurred under age 40 years (OR, 7.5; 95% CI, 2.6-21.4). This effect remained when evaluating menopausal status 10 years before diagnosis. There was no association with parity overall, but risk was increased for first childbirth under age 20 years compared with nulliparity (OR, 3.4; 95% CI, 1.4-8.4). No significant association was observed with ever use of oral contraceptives or hormone replacement therapy, nor with cigarette smoking, past head injury, past diagnosis with epilepsy, or birth characteristics, except for an inverse association of risk with maternal age. This study suggests a raised risk of pituitary tumors in relation to surgically induced menopause, early postmenopausal age, and young age at childbirth, and possibly a reduced risk with hay fever and increasing maternal age. Reasons for these associations need further investigation, but some associations might be due to hormonal effects of an undiagnosed pituitary tumor.