Several lines of evidence indicate a potential role for hormonal or reproductive factors in the subsequent development of large bowel cancer in women. To evaluate the relationship between hormone exposure and large bowel cancer a case-control study was carried out in 18 Illinois hospitals. Female cases, ages 45-74 (n = 90), and controls (n = 208) were identified from an ongoing large bowel cancer study. Data were obtained from medical records, personal interviews, and a subsequent mail survey with a questionnaire specific to hormone usage. Menopausal estrogen use was found to be protective with respect to the subsequent development of large bowel cancer with an odds ratio of 0.6 (95% CI, 0.33-0.99). This effect remained after controlling individually for age at diagnosis, ever pregnant (yes/no), parity, age at first birth, hysterectomy with documented oophorectomy, cholecystectomy, and appendectomy. Simultaneous adjustment, using logistic regression, for age at diagnosis, parity, hysterectomy, and cholecystectomy resulted in an adjusted odds ratio for menopausal estrogen use and large bowel cancer of 0.5 (95% CI, 0.27-0.90). Subsite analysis revealed the protective effect to be strongest for the rectal cancer cases. These data support the hypothesis that exogenous hormones may alter the risk of large bowel cancer in women.