Polybrominated diphenyl ethers (PBDEs) are a group of chemicals widely used as flame retardants; the lower brominated forms (1-5 bromine atoms) are highly neurotoxic and are presently not in commercial use. The highest brominated, the decabromodiphenyl ether (BDE-209) remains in use and its adverse and persistent effects are subject to debate. Of special concern are developmental exposures that can disrupt later-in-life adult health or aging. In this study, we investigated the effects of postnatal exposure to BDE-209 in combination with apolipoprotein E (apoE) genotype, a genetic factor that is associated with varied vulnerability for the development of neurodegenerative diseases. On postnatal day 10, transgenic mice of both sexes carrying apoE2, apoE3 and apoE4 were orally exposed to 0, 10 or 30mg/kg of BDE-209. Spatial reference memory was assessed in a Morris Water Maze (MWM) task at 4 and 12months of age. The levels of the brain-derived neurotrophic factor (BDNF) were determined in hippocampus and frontal cortex of mice at 5months of age. Mice carrying different apoE polymorphisms showed differences in the acquisition and retention of the spatial navigation task both at 4 and 12months of age. Postnatal exposure to BDE-209 induced long term effects in spatial learning, which were dependent upon age, sex and apoE genotype; these effects were more evident in apoE3 mice. BDNF levels were lower in the frontal cortex of apoE4 mice and higher in the hippocampus of exposed mice, independent of the genotype. The results of the present study provide evidence of long-lasting effects in spatial learning and memory after early exposure to BDE-209. Developmental exposure to this neurotoxicant may contribute to cognitive decline and abnormal aging.