Background/Aim: Exposure to combinations of chemical neurotoxicants has not been well explored as a risk factor for mental health difficulties. We evaluated associations of prenatal exposure to mixtures of organochlorines and metals with adolescent internalizing behaviors.Methods: Participants were 397 socioeconomically (32% household income <$20,000) and racially (31% non-White) diverse children from a prospective birth cohort recruited at birth (1993-1998) in New Bedford, Massachusetts. Organochlorines [hexachlorobenzene, p,p'-dichlorodiphenyl dichloroethylene, polychlorinated biphenyls] and metals [manganese, lead] were analyzed in cord blood. Internalizing behaviors (anxiety, depression, somatization) at age ~15 years were assessed via teacher, parent, and self-report using the Behavior Assessment System for Children, 2nd Edition (BASC-2). Adjusted for sociodemographic predictors of exposures and internalizing behaviors, multi-chemical linear regression and Bayesian Kernel Machine Regression (BKMR) were used to explore overall and sex-specific associations between prenatal chemical exposures and BASC-2 T-scores [standardized to mean (standard deviation) of 50 (10)].Results: Chemical concentrations were consistent with background exposure levels [e.g., mean (range) cord blood lead: 1.50 (0-17.45) g/dL]. Although there was some variability in magnitude and precision, across all three reporters, lead was associated with higher anxiety, depression, and somatization behaviors in adolescents of both sexes. For example, in linear regression, a doubling of lead was associated with a 1.6-point higher (95% confidence interval: 0.6, 2.7) parent-reported anxiety T-score. There was suggestive evidence of increased susceptibility to lead among boys for parent-reported behaviors. The direction of associations of organochlorines and manganese with internalizing behaviors varied, depending on the reporter. BKMR analysis supported linear regression results, with no evidence of interactions between chemicals or non-linear associations.Conclusions: Low-level prenatal lead exposure was consistently associated with adolescent internalizing behaviors. In utero chemical exposures, particularly lead, may contribute to the emergence of anxiety and depression symptoms during this vulnerable developmental stage.[Funding: NIEHS/NIH P42ES005947, R01ES014864; CDC/NIOSH T42OH008416].