OBJECTIVE: To evaluate whether children of parents with the insulin resistance syndrome (IRS) themselves have greater insulin resistance and unfavorable patterns of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS: This cross-sectional study included 220 white and 36 black children aged 11-15 years identified through a school-based blood pressure screening program, along with 378 of their parents. Measures of insulin resistance (glucose disposal per minute per kilogram of lean body mass in a euglycemic-hyperinsulinemic clamp [Mlbm] and fasting insulin), adiposity, and other CVD risk factors were compared in children with and without a parental history of IRS, defined according to the National Cholesterol Education Program Adult Treatment Panel III consensus definition. RESULTS: Compared with children in whom neither parent had IRS, children who had at least one parent with the syndrome had statistically significantly lower mean Mlbm (12.1 vs. 13.6 mg.kg(-1).min(-1); P=0.04) and higher fasting insulin (geometric means 99 vs. 76 pmol/l; P=0.01) after adjustment for sex, race, age, and Tanner stage. Mean BMI, waist circumference, waist-to-hip ratio, triceps and subscapular skinfolds, and percentage of body fat were also significantly higher in children of an affected parent, but there were no significant differences in lipid or blood pressure levels between the two groups. CONCLUSIONS: Insulin resistance and obesity may be the earliest manifestations of IRS in children with a parental history of the syndrome.