Polyhalogenated biphenyls induce microsomal mixed-function oxygenases in many species including man. They can be divided into two classes of inducers. 3,4,5,3',4', 5'-Hexa- and 3,4,3',4'-tetrachlorobiphenyls appear to interact with the TCDD receptor, albeit at 100 to 1,000 times the dose. The structure required for 3-MC (TCDD)-type induction seems to be the presence of at least two adjacent halogens in the lateral positions (meta and para) of the benzene rings, and an absence of halogens in the ortho positions adjacent to the biphenyl bridge. It is likely that halogenation of the ortho positions prevents binding by blocking planar configuration. These isomers, although less toxic than TCDD, are much more toxic than other PCB isomers. Most halogenated biphenyl isomers are phenobarbital type inducers or are inactive. The structure-activity relationship for this type of induction is less clear, but active isomers include 2,4,2',4'-tetra-; 2,4,5,2',4',5'-; 2,3,4,2',3',4'-; 2,3,5,2',3'.5'-and 2,4,6,2',4',6'-hexachlorobiphenyls and 2,4,5,2',4',5'-hexabromobiphenyl. The inactivity of many of the lower chlorinated isomers as inducers (mono-through tetrachloro-) may be related to their rapid metabolism. The cytochrome which is induced by commercial PCB and PBB mixtures appears to be identical to a mixture of cytochromes from phenobarbital- and 3-MC-treated rats. These structure-activity relationships suggest that the "mixed inductive" effects and much of the toxicity of PCB and PBB mixtures are due to the presence of compounds related structurally to the active chlorinated dibenzofurans or 3,4,3',4'-tetrachlorobiphenyl.