Putative protective effects of selenium (Se) against methylmercury (MeHg) toxicity have been examined but no conclusion has been reached. We recently reported the lack of serious neurological symptoms in a Japanese fish-eating population with high intakes of MeHg and suggested a potential protective role for Se. Here, relationships between levels of Hg and Se in the blood and plasma samples, with a quantitative evaluation of Se-containing proteins, obtained from this population were examined. While levels of the whole-blood Hg (WB-Hg) and plasma Se (P-Se) showed a positive correlation, stratified analysis revealed that they correlated only in samples with higher (greater than the median) levels of MeHg. A food frequency questionnaire showed that consumption of fish/whales correlated with WB-Hg, but not with P-Se, suggesting that the positive correlation between WB-Hg and P-Se might not be the result of cointake of these elements from seafood. Speciation of plasma Se revealed the differences in the responses of two plasma selenoproteins, glutathione peroxidase (GPx) and selenoprotein P (SePP), in relation to Hg exposure. In the high-Hg group, SePP showed a positive correlation with WB-Hg, but GPx did not. In the low-Hg group, neither SePP nor GPx showed any correlation with WB-Hg. These observations suggest that the increase in P-Se in the high-Hg group might be associated with an increase in SePP, which may, in turn, suggest an increased demand for one or more selenoproteins in various organs, for which SePP supplies the element. (C) 2016 Elsevier Ireland Ltd. All rights reserved.