A high level of endogenous estrogen in utero has been hypothesized to he a possible risk factor for breast cancer. We used information from two population-hosed case-control studies to investigate the relation between perinatal factors and risk of invasive breast cancer among women age 21–45 years (746 cases, 960 controls) and women age 50–64 years (401 cases, 439 controls). Breast cancer cases were ascertained through a population-based cancer registry, and controls were selected by random digit dialing. After adjustment for age, menopausal status, and maternal smoking, the birthweight-breast cancer association in women age 21–45 years followed a J-shaped curve, with women whose birthweight was less than 2,500 gm [odds ratio (OR) = 1.3; 95.4, confidence interval (CI) = 09–2.01 and 4,000 gm or more (OR = 1.7; 95% CI = 1.1–2.5) at increased risk. Women age 50–64 years who were 4,000 gm or more at birth appeared to be at slightly reduced risk of breast cancer (OR = 0.6; 95% CI = 0.3–1.1). With the exception of maternal smirking, there was little effect of other perinatal factors on breast cancer risk in either group. These results support the hypothesized association between intrauterine estrogen exposure and subsequent risk of breast cancer.