The interaction between methylmercury (MeHg) and marine fatty acids is of great interest in risk benefit assessments, and is increasingly important also in fish nutrition when fish oil is replaced with vegetable oils. To assess the effects of replacing fish oil (high dietary n-3/n-6 ratio) by soybean oil (low dietary n-3/n-6 ratio) in combination with MeHg, Atlantic salmon (Salmo salar L.) were fed experimental diets (fish oil (FO) or vegetable oil (VO) based, with or without the addition of MeHg) for 3 months. As expected replacing dietary fish oil by soybean oil had greater effect on the fatty acid composition in white muscle compared to brain. In brain, the relative levels of 18:2 n-6 and 20:4 n-6 increased in all lipid classes in fish fed the VO based diets whereas the levels of marine omega-3 PUFA (polyunsaturated fatty acid) were unaffected. Different dietary lipid sources did not affect the accumulation of mercury in brain nor muscle. However, exposure to dietary MeHg resulted in decreased levels of 20:4 n-6 (arachidonic acid; ARA) in phosphatidylinositol in brain of VO fed fish. The decreased amounts of ARA in VO fish is suggested to be caused by interaction between high n-6 level and MeHg.