Due to the extremely high affinity of selenium (Se) to mercury (Hg), Se sequesters Hg and reduces its biological availability in organisms. However the converse is also true. Hg sequesters Se, causing Hg to inhibit the formation of Se dependent enzymes while supplemental Se supports their continued synthesis. Hence, whether or not toxic effects accompany exposure to Hg depends upon the tissue Se:Hg molar ratio of the organism. The main objective of the present study was to investigate how levels of Hg and Se affected metallothionein (MT) induction in free-ranging brown trout, Salmo trutta, from Lake Mjøsa, Norway (a Se depauperate lake). MT is proposed as a sensitive biomarker of potential detrimental effects induced by metals such as Hg. Emphasis was addressed to elucidate if increased tissue Se:Hg molar ratios and Se levels affected the demands for MT in the trout. The Se:Hg molar ratio followed by tissue Se levels were most successful for assessing the relationship between metal exposure and MT levels in the trout. Thus, Hg in molar excess over Se was a stronger inducer of MT synthesis than tissue Hg levels in the trout, supporting the assumption that Se has a prominent protective effect against Hg toxicity. Measuring Hg in animals may therefore provide an inadequate reflection of the potential health risks to humans and wildlife if the protective effects of Se are not considered.