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To assess the relationships between childhood lead exposure and 3 domains of later adolescent health: mental, physical, and behavioral.We followed a random sample of birth cohort members from the Project on Human Development in Chicago Neighborhoods, recruited in 1995 to 1997, to age 17 years and matched to childhood blood test results from the Department of Public Health. We used ordinary least squares regression, coarsened exact matching, and instrumental variables to assess the relationship between average blood lead levels in childhood and impulsivity, anxiety or depression, and body mass index in adolescence. All models adjusted for relevant individual, household, and neighborhood characteristics.After adjustment, a 1 microgram per deciliter increase in average childhood blood lead level significantly predicts 0.06 (95% confidence interval [CI] = 0.01, 0.12) and 0.09 (95% CI = 0.03, 0.16) SD increases and a 0.37 (95% CI = 0.11, 0.64) point increase in adolescent impulsivity, anxiety or depression, and body mass index, respectively, following ordinary least squares regression. Results following matching and instrumental variable strategies are very similar.Childhood lead exposure undermines adolescent well-being, with implications for the persistence of racial and class inequalities, considering structural patterns of initial exposure.