A case-control study, conducted among participants in the Breast Cancer Detection Demonstration Project, obtained detailed information on family history of breast cancer and other risk factors from 1,362 breast cancer patients and 1,250 control subjects. An affected first-degree relative was reported by 22.4% of the patients and 12.2% of the control subjects. This finding was associated with a twofold increased risk of breast cancer, although greater elevations in risk were seen in younger study subjects and in those reporting both an affected mother and a sister. Analysis of other risk factors showed that, compared to women without a family history of breast cancer, control subjects with a family history of breast cancer tended to have early or late menarche, were older at first childbirth, and were younger at oophorectomy. In addition, the effect of family history on breast cancer risk was modified by age at menarche, but not by age at first birth or type of menopause. These findings suggest that familial susceptibility to breast cancer may be mediated through hormonal factors that operate early in a woman's life. A synergistic relationship was also observed between family history of breast cancer and the occurrence of multiple biopsies for benign breast disease, although the mechanisms for this relationship remain to be elucidated.