OBJECTIVE: To examine the effects of low birth weight (LBW) on the components of insulin resistance syndrome (IRS) in Caucasian and African-American children aged 4-14 years (n = 560 observations among 139 subjects). RESEARCH DESIGN AND METHODS: A linear random-effects modeling analysis with repeated measures (average four annual visits per child) was conducted to examine the associations between LBW and the components of IRS and their developmental trends over age. Fasting glucose, insulin, and lipids were assessed after an overnight fast; insulin action and secretion were determined by the tolbutamide-modified frequently sampled intravenous glucose tolerance test; and body composition was assessed by dual energy X-ray absorptiometry and computed tomography. RESULTS: LBW was significantly associated with increased fasting insulin concentration and visceral fat mass, decreased acute insulin response, beta-cell function, and HDL cholesterol among African-American children. Among children with LBW, there were significant differences in fasting insulin, insulin sensitivity, acute insulin response, and HDL cholesterol between Caucasians and African-Americans. LBW was significantly associated with faster decrease in acute insulin response and increase in triglycerides with regard to age. The hyperbolic function between insulin sensitivity and beta-cell function was retarded among children with LBW (P = 0.04). In addition, there was a significant interaction between LBW and ethnicity in relation to fasting insulin (P < 0.05) and visceral fat (P = 0.05). CONCLUSIONS: LBW may predict the risk of the IRS and its progression over age in childhood, and this effect may be more pronounced among African-American children.