Inorganic arsenic intake in 969 men and women and methylmercury intake in 785 men and women from across the United States were assessed by a semiquantitative food frequency questionnaire, in combination with a database for the content of those elements in foods, and by toenail concentrations of arsenic and mercury. In addition, empirical weights for foods on the dietary questionnaire were derived from multivariate regression models to estimate associations between diet and toenail arsenic and mercury levels, independent of the assumptions about inorganic arsenic and methylmercury in foods, which are based upon limited residue measurements. The use of empirical weights significantly improved the correlation of arsenic consumption with toenail arsenic levels (r = 0.33, P = 0.0001), compared with the weak correlation obtained using the food residue method to calculate intake (r = 0.15, P = 0.0001). Mercury consumption computed using empirical weights yielded a significant correlation with toenail arsenic (r = 0.42, P = 0.001), similar to the correlation using energy-adjusted intake calculated from food residue tables (r = 0.35, P = 0.001). These results illustrate the potential use of empirically derived weights for foods in estimating toenail levels of selected heavy metals and support the validity of published food residue data that are used to estimate mercury consumption.