OBJECTIVE To compare energy intake derived from a food frequency questionnaire (FFQ) with estimated energy expenditure in postmenopausal women participating in a large clinical study. METHODS A total of 161,856 women aged 50 to 79 years enrolled in the Women's Health Initiative (WHI) Observational Study (OS) or Clinical Trial (CT) [including the Diet Modification (DM) component] completed the WHI FFQ, from which energy intake (FFQEI) was derived. Population-adjusted total energy expenditure (PATEE) was calculated according to the Harris-Benedict equation weighted by caloric intakes derived from the National Health and Nutrition Examination Survey. Stepwise regression was used to examine the influence of independent variables (e.g., demographic, anthropometric) on FFQEI-PATEE. Race, region, and education were forced into the model; other variables were retained if they increased model explanatory ability by more than 1%. RESULTS On average, FFQEI was approximately 25% lower than PATEE. Regression results (intercept=-799 kcal/d) indicated that body mass index (b=-23 kcal/day/kg.m(-2)); age (b=15 kcal/day/year of age); and study arm (relative to women in the OS, for DM women b=169 kcal/d, indicating better agreement with PATEE) increased model partial R(2)>.01. Results for CT women not eligible for DM were similar to those of women in the OS (b=14 kcal/d). There also were apparent differences by race (b=-152 kcal/d in Blacks) and education (b=-67 kcal/d in women with<high school). CONCLUSIONS This large, carefully studied population confirms previous observations regarding underestimates in self-reported caloric intake relative to estimates of metabolic need in younger women, and those with higher weight, with less education, and in Blacks. These differences, along with effects related to intervention assignment, underline the need for additional research to enhance understanding of errors in dietary measurement.