African-American women are heavier than European-American women; the reasons are unknown. The purpose of this study was to examine potentially modifiable reasons for the weight difference among 86,326 female nurses. The determinants of body mass index (BMI) were modelled using the method of linear regression. The findings included the following: mean BMI (kg/m2) was 9.0% (95% CI, 7.8-10.1%) higher among African American (27.3) than among European-American women (25.1) (P<0.0001). However, recalled BMI at age 18 was equal in the two groups (21.4, P=0.98). Multivariate determinants of BMI include age, age 18 BMI, alcohol and calorie intake, exercise, marital status, parity, race, recent intentional weight loss, smoking, and television watching. Even after controlling for these factors, African-American women still had an 8.6% (95% CI, 7.7-9.5%) higher BMI than European-American women. Correction for error in measurement of physical activity attenuated this difference to 6.4% (95% CI, 5.0-7.8%). In conclusion, in this single occupation group, African-American women had a significantly higher BMI than European-American women. Age and measured behavioral factors did not explain this difference. However, imprecision in the measurement of diet and activity may explain this difference in part. Better measurement may help quantify the differences that are as yet unexplained.