By means of IC-ICP/MS, different valence states of arsenic and mercury in the form of inorganic and organic species can be sensitively and unambiguously identified in one single run. Determination of common arsenic species in biological matrices is straightforward and can be performed down to the sub-ppb level.Species transformations of mercury that occur during several sample preparation techniques, however, require the use of specific isotope dilution mass spectrometry (SIDMS). This work illustrates the decisive advantage that Environmental Protection Agency (EPA) Method 6800 (SIDMS) offers for studying the transformations of mercury species during sample preparation of fish tissue samples. Because of the unique features and benefits of EPA Method 6800, it is expected that utilization of SIDMS will increase and that this valuable tool for optimizing and validating trace-metals-speciated sample preparation will gain much wider acceptance by analytical chemists.