Blood serum is one of the more viable matrices used in assessing exposure to persistent environmental contaminants or their metabolites, especially those that are lipophilic. Analytic methods currently in use for this matrix usually involve liquid/liquid extraction followed by adsorption chromatography as a cleanup step, and low- or high-resolution gas chromatography with either electron-capture or mass spectrometric detection. The traditional analytic methods are labor intensive, have low sample throughput, and use excessive amounts of solvents and reagents. Two analytic approaches that address the requirements of modern laboratories more effectively are: 1) solid-phase extraction (SPE), used to analyze serum for several classes of compounds of environmental concern (e.g., polychlorinated biphenyls [PCBs], persistent pesticides, dioxins, furans, and coplanar polychlorinated biphenyls [CPCBs]), and 2) fast chromatography with a two-dimensional gas chromatographic system, which can be used in the determinative step for these types of analytes.