Although the elevation of circulating total serum homocysteine (tHcy) concentration in a fasting state is associated with an increased risk of occlusive vascular disease in adults, the implications of elevated levels in children are not known. The goals of this study were to describe the distribution of tHcy among a representative sample of children and adolescents in the United States, and to test for differences in tHcy among sex, age and race-ethnicity categories. Using surplus sera from Phase 2 of the third National Health and Nutrition Examination Survey, we measured tHcy for a nationally representative sample of 942 boys and 1085 girls aged 4-19 y. The age-adjusted geometric mean tHcy concentrations were 6.2 and 5.8 micro mol/L in non-Hispanic Caucasian boys and girls, 6.4 and 6.1 micro mol/L in non-Hispanic African-American boys and girls, and 6.4 and 5.5 micro mol/L in Mexican American boys and girls, respectively. A significant interaction between age and sex (P < 0.01) reflected the divergence of tHcy concentrations at about age 10 y, with higher concentrations in boys than in girls throughout adolescence. These first data on homocysteine concentrations in a nationally representative sample of American youth suggest that sexual dimorphism of tHcy concentrations occurs earlier, at approximately 10 y of age, than previously reported on the basis of smaller nonrepresentative samples. Improved understanding of the determinants of levels during growth and development may provide important clues to the etiology of adult disease.