Background: Family history of breast cancer is an established risk factor for this disease and is used to identify women at higher risk, although the impact of risk factors for breast cancer among women with a family history is not well defined. Purpose: Using a modified extended log-incidence Pike model, we prospectively examined the impact of risk factors for breast cancer among women with and without a family history of the disease. Methods: Data analyzed were obtained prospectively from the Nurses' Health Study. Two thousand two hundred forty-nine incident cases of invasive breast cancer were identified in a cohort of 89 132 women aged 30-55 years in 1976 followed biennially through 1990 (1.1 million person-years of follow-up). With the use of proportional hazards models, we evaluated the association between risk factors for breast cancer and risk among women with and those without a family history of the disease. We then fit a modified extended log-incidence Pike model to these data. Results: Among women with a family history of breast cancer, reproductive risk factors had associations that were different from those observed among women without a family history of the disease. In particular, we observed little protection from later age at menarche, no protection from multiple births when compared with nulliparity, nor from early, as compared with later, age at first birth. Fitting these data to a model of breast cancer incidence on the basis of reproductive risk factors, we observed an adverse effect of first pregnancy on risk of breast cancer among women with a family history of breast cancer that was approximately 50% greater in magnitude than among women without a family history. Additional births after the first birth conveyed little protection for women with a family history. History of benign breast disease, past use of oral contraceptives, and use of postmenopausal hormones showed relative risks that did not differ between women with a family history and those without a family history of the disease. Conclusions: We observed a consistent increase in risk of breast cancer among women with a mother or sister history of the disease that was exacerbated by first pregnancy. Among women with a family history of breast cancer, the adverse effect of pregnancy persisted so that to age 70 years, parous women were at higher risk of breast cancer than nulliparous women. Among women without a family history of the disease, first pregnancy was associated with a smaller increase in risk, and early pregnancy and higher number of births were each associated with reduced breast cancer incidence.