Identification of lipophilic chemicals requires the development of new techniques to detect these compounds at the cellular and subcellular levels. To address this issue, we have developed a combinational protocol using antibodies directed against chemicals together with a multiple signal amplification system (catalyzed signal amplification/gold-substituted silver-intensified peroxidase) to detect the lipophilic compounds at their subcellular sites of accumulation by transmission electron microscopy. As a model organism, we exposed the blue mussel Mytilus edulis to the polycyclic aromatic hydrocarbon phenanthrene and the polychlorinated biphenyl mixture Aroclor 1254 for up to 10 d. The aim of these exposure experiments was to analyze the cellular targets and sites of accumulation in the digestive system by transmission electron microscopy. The endo-lysosomal system of digestive cells and mitochondria of epithelial cells appeared to be the preferred accumulation sites for the lipophilic compounds studied. The antibody-based approach to detect lipophilic chemicals provides an important insight into the pathways of uptake and accumulation as well as mechanisms of toxicity.