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Background: Hemoglobin and erythrocyte protoporphyrin (EP) tests are commonly used to screen for iron deficiency. However, little research has been done to systematically evaluate the sensitivity and specificity of these 2 tests. Objective: The objective of this study was to evaluate the sensitivity and specificity of hemoglobin and EP measurements in predicting iron deficiency in preschool children and in women of childbearing age. Design: We examined data from the third National Health and Nutrition Examination Survey (n = 2613 children aged 1-5 y and n = 5175 nonpregnant women aged 15-49 y). Children or women with blood lead [greater than or equal to] 10 [micro]g/dL were excluded from this study. We used the receiver operating characteristic (ROC) curve to characterize the sensitivity and specificity of hemoglobin and EP measurements in screening for iron deficiency, defined as having abnormal values for [greater than or equal to] 2 of the following 3 indexes: mean cell volume, transferrin saturation, and serum ferritin. Results: The ROC performance of EP was consistently better than that of hemoglobin for detecting iron deficiency in preschool children. However, in nonpregnant women, we found no significant difference between EP and hemoglobin in ROC performance for detecting iron deficiency. We observed the same results when we stratified the analyses by sex and race of the children and by race of the women. Conclusions: For children aged 1-5 y, EP is a better screening tool for iron deficiency than is hemoglobin. However, for nonpregnant women, EP and hemoglobin have similar sensitivity and specificity for predicting iron deficiency. Am J Clin Nutr 2003;77:1229-33. KEY WORDS Iron deficiency, hemoglobin, erythrocyte protoporphyrin, zinc protoporphyrin, mean cell volume, transferrin saturation, serum ferritin, receiver operating characteristic curve, preschool children, women, iron deficiency anemia