Some chemicals released into the environment, including mercury and some organochlorine compounds (OCs), are suspected to have a key role on subclinical brain dysfunction in childhood. Alteration of the glutamatergic system may be one mechanistic pathway. We aimed to determine whether mercury and seven OCs, including PCBs 138, 153, and 180, DDT and DDE, hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (β-HCH) influence the cord levels of two excitatory amino acids, glutamate and aspartate. Second, we evaluated if this association was mediated by glutamate uptake measured in human placental membranes. The study sample included 40 newborns from a Spanish cohort selected according to cord mercury levels. We determined the content of both amino acids in cord blood samples by means of HPLC and assessed their associations with the contaminants using linear regression analyses, and the effect of the contaminants on glutamate uptake by means of [3H]-aspartate binding in human placenta samples. PCB138, β-HCH, and the sum of the three PCBs and seven OCs showed a significant negative association with glutamate levels (decrease of 51, 24, 56 and 54%, respectively, in glutamate levels for each 10-fold increase in the contaminant concentration). Mercury did not show a significant correlation neither with glutamate nor aspartate levels in cord blood, however a compensatory effect between T-Hg and both PCB138, and 4,4'-DDE was observed. The organo-metallic derivative methylmercury completely inhibited glutamate uptake in placenta while PCB138 and β-HCH partially inhibited it (IC50 values: 4.9±0.8μM, 14.2±1.2nM and 6.9±2.9nM, respectively). We conclude that some environmental toxicants may alter the glutamate content in the umbilical cord blood, which might underlie alterations in human development. ; a Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Barcelona, Spain b CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain c Center for Public Health Research (CSISP-FISABIO), Valencia, Spain d Institute of Environmental Assessment and Water Research (IDÆA-CSIC), Barcelona, Spain e University of Valencia, Valencia, Spain