AbstractThe effects of pretreatment with symmetrically dihalogenated biphenyls (DXBs, X‐F, Cl(C), Br(B) and I) on rat liver drug metabolism enzymes were investigated. 4,4′‐DFB, ‐DCB, and ‐DBB as well as 2,2′‐DFB appeared to be inducers of microsomal cytochrome P‐450‐linked monoxygenases (N‐demethylases of aminopyrine and ethylmorphine). However, no structure‐induction relationship was found. 4,4′‐DXBs also induced a cytochrome P‐448‐linked mono‐oxygenase (ethoxyre‐sorufinO‐deethylase), and their order of induction potential seemed to parallel the increase of the size of the halogen substituent. Therefore, 4,4′‐DXB's may be categorized as mixed‐type inducers, the cytochrome P‐450 component being the more pronounced. Data on the cytochrome P‐448 induction by dihalogenated biphenyls with only para substituents may be considered as a refinement of the previously described structure‐activity relationship in this respect. All of the DXBs except 3,3′‐DCB and 4,4′‐DIB, enhanced, like phenobarbital, the activity of UDP‐glucuronyltransferase toward 4‐hydroxybiphenyl. Only 4,4′‐DFB was able to induce the activity of glutathione S‐transferase toward 1,2‐epoxy‐3‐(p‐nitrophenoxy)propane. Studies after 4,4′‐DBB‐treatment revealed, like phenobarbital, a preferential induction of ethylmorphineN‐demethylase on rough endoplasmic reticulum‐derived microsomes, whereas UDP‐glucuronyltransferase activity toward 4‐hydroxybiphenyl was induced to a larger extent on smooth endoplasmic re