Mammographically defined percent breast density is an important risk factor for breast cancer, but the epidemiology of this trait is poorly understood. Although several studies have investigated the associations between reproductive factors and density, few data are available on the associations of breast density and waist-to-hip ratio (WHR), physical activity, education, alcohol and smoking. We investigated the associations of known and suspected breast cancer risk factors with breast density in a large breast cancer family study. Information was collected on members of 426 families through telephone interviews, mailed questionnaires and mammography. Mammographic films on 1900 women were digitized and breast density was estimated in discrete five-unit increments by one radiologist. Analysis of covariance techniques were used and all analyses were performed stratified by menopausal status. Similar to other reports, nulliparity, late age at first birth, younger age and lower body mass index were associated with increased percent density in both premenopausal and postmenopausal women, and hormone replacement therapy among postmenopausal women. Higher levels of alcohol consumption and low WHR were associated with increased percent density among both premenopausal and postmenopausal women (differences of 3-11% between high and low categories). However, smoking and education were inversely associated with percent density among premenopausal (p = 0.004 and p = 0.003, respectively) but not postmenopausal women (p = 0.52 and p = 0.90). Physical activity was not associated with percent density in either stratum (p values > 0.25). Combined, these factors explained approximately 37% of the variability in the percent density measure in premenopausal women and 19% in postmenopausal women. Many of these factors may potentially affect breast cancer risk through their effect on percent breast density.