Proliferative benign breast disease is a marker of increased breast cancer risk, yet little is known about its etiology. Most studies of benign breast disease have focused only on risk factors in adulthood, despite growing evidence that factors in early life influence breast cancer risk. We explored the relations of several early life factors with incidence of proliferative benign breast disease among 71,896 premenopausal women in the Nurses' Health Study II who recalled their body fatness at young ages, physical activity in adolescence, birthweight, and history of being breastfed. Between 1991 and 1997, 901 of these women were identified as having proliferative benign breast disease from a centralized pathology review. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazards models. Greater childhood body fatness (ages 5-10) was associated with decreased risk of proliferative benign breast disease; the multivariate RR (95% CI) for the most overweight compared with the most lean was 0.61 (0.44-0.86; P(trend) < 0.0001) and remained significant after adjustment for current body mass index. Body mass index at age 18 was also inversely associated with incidence of proliferative benign breast disease, with a multivariate RR (95% CI) of 0.67 (0.52-0.88) for those who were > or =25 kg/m(2) compared with those who were <19 kg/m(2) (P(trend) = 0.001). There were no clear associations for physical activity in adolescence, birthweight, or being breastfed. These results indicate that premenopausal women who were heavier at young ages have lower incidence of proliferative benign breast disease, consistent with previous findings for breast cancer.