Adolescent obesity is a strong predictor of adult obesity, and adult obesity has been associated with depression, especially in women. Studies have also suggested an association between depression in adolescence and higher body mass index (BMI) in adulthood. Whether depression leads to obesity or obesity causes depression is unclear. To determine in longitudinal analyses whether depressed mood predicts the development and persistence of obesity in adolescents. A prospective cohort study of 9374 adolescents in grades 7 through 12 who completed in-home interviews for the National Longitudinal Study of Adolescent Health. Assessments were made at baseline (1995) and at follow-up 1 year later. Depressed mood was assessed with the Center for Epidemiologic Studies Depression Scale. BMI (kg/m2) was calculated from self-reported height and weight. BMI percentiles and z scores were computed using the 2000 Centers for Disease Control and Prevention growth charts. Obesity was defined as BMI > or =95th percentile, overweight as BMI > or =85th percentile and <95th percentile, and normal weight as BMI <85th percentile. A parental respondent gave information on household income, parental education, and parental obesity. At baseline, 12.9% were overweight, 9.7% were obese, and 8.8% had depressed mood. Baseline depression was not significantly correlated with baseline obesity. Among the 9.7% who were obese at follow-up, 79.6% were obese at baseline, 18.6% were overweight at baseline, and 1.8% were normal weight at baseline. Having depressed mood at baseline independently predicted obesity at follow-up (odds ratio: 2.05; 95% confidence interval: 1.18, 3.56) after controlling for BMI z score at baseline, age, race, gender, parental obesity, number of parents in the home, and family socioeconomic status. This finding persisted after controlling further for the adolescents' report of smoking, self-esteem, delinquent behavior (conduct disorder), and physical activity. After controlling for all these same factors, depressed mood at baseline also predicted obesity at follow-up among those not obese at baseline (odds ratio: 2.05; 95% confidence interval: 1.04, 4.06) and follow-up BMI z score among those obese at baseline (beta = 0.11; standard error beta = 0.05). In contrast, baseline obesity did not predict follow-up depression. Depressed adolescents are at increased risk for the development and persistence of obesity during adolescence. Understanding the shared biological and social determinants linking depressed mood and obesity may inform the prevention and treatment of both disorders.