Polychlorinated and polybrominated biphenyls are industrial chemical mixtures which have been implicated in numerous human poisonings in Taiwan and Japan (PCBs) and Michigan (PBBs). Moreover, these polyhalogenated biphenyls have been widely detected in the environment including the air, water, fish, wildlife, human adipose tissue, and blood and breast milk. A major problem associated with the analysis and toxicology of this group of chemicals is their chemical complexity (e.g., there are 209 possible PCB isomers and congeners) and the remarkable effects of structure on activity. This article will discuss the effects of structure on the biologic and toxic effects of individual PCB and PBB congeners as well as reconstituted mixtures. The results clearly show that like "dioxin" (or 2,3,7,8-TCDD), the PCBs and PBBs elicit their effects through a cytosolic receptor protein which preferentially binds with the toxins which are approximate isostereomers of 2,3,7,8-TCDD. The evidence for this mechanism of action will be discussed in detail.