Insulin resistance and obesity are associated in children as they are in adults. However, although insulin resistance seems to oppose further weight gain in adults, opposite results have been found in children. To investigate the relationship between childhood obesity, insulin resistance, and long-term weight gain, we selected 215 obese Caucasian children (120 males and 95 females) aged 10.5 (+/-2.4) yr, with a relative body mass index (BMI) of 153.8% (+/-27.7%) and normal glucose tolerance. Insulin resistance was assessed at baseline by using the homeostasis model assessment. Fourteen (+/-5) years later, 103 subjects returned for a follow-up examination of height and weight. At follow-up, 37 subjects (36%) were obese (BMI > or = 30), 33 (32%) were overweight (25 < or = BMI < 30), and 33 (32%) were of normal weight (20 < or = BMI < 25). In a multiple regression, relative BMI and insulin resistance at childhood were independent predictors of adulthood BMI (r(2) = 0.44; P < 0.01) in girls. A multivariate logistic regression analysis showed that high relative BMI [odds ratio, 1.06; 95% confidence interval, 1.00-1.13; P = 0.04] and low insulin resistance index at baseline (odds ratio, 0.58; 95% confidence interval, 0.34-0.99; P = 0.04) predicted obesity in adulthood for girls, no matter their age, Tanner stage, and their parents' BMI. In boys, insulin resistance was not a significant predictor of adult obesity. In conclusion, obesity tracks into adulthood for many obese Caucasian children. In obese girls, insulin resistance during childhood appears to oppose the risk of obesity in adulthood.