Methylmercury (MeHg) is an environmental neurotoxicant with adverse effects particularly noted in the developing brain. The main source of MeHg exposure is seafood. However, fish is also an important source of n-3 fatty acids such as docosahexaenoic acid (DHA) which has neuroprotective effects, and which plays an important role during the prenatal development of the central nervous system. The aim of the present study was to examine the effects of DHA and MeHg individually, and in combination, on development using accumulation, behavioural and transcriptomic endpoints in a mammalian model. Analyses were performed on 15 day old mice which had been exposed to varying levels of DHA (8 or 24 mg/kg) and/or MeHg (4 mg/kg) throughout development via the maternal diet. Supplementation of the maternal diet with DHA reduced MeHg accumulation in the brain. An accelerated development of grasping reflex was seen in mice offspring in the 'MeHg + high DHA' group when compared to 'MeHg' and 'control'. Exposure to MeHg and DHA had an impact on cerebral gene expression as assessed by microarray and qPCR analysis. The results from the present study show the potential of DHA for alleviating toxicity caused by MeHg. This information may contribute towards refining risk/benefit assessment of seafood consumption and may enhance understanding of discrepancies between epidemiological studies of MeHg neurodevelopmental toxicity. (C) 2011 Elsevier B.V. All rights reserved.