We studied the effect of triphenyldioxane on phase I xenobiotic metabolism enzymes in the liver of rats and rabbits. Total cytochrome P450 content, protein concentration, and catalytic activity of CYP2B, CYP3A, and CYP2C isoforms were measured. Triphenyldioxane significantly increases specific activity of CYP2B and CYP2C in the liver of rats and rabbits, respectively. Immunoblotting analysis of microsomal enzymes in the liver of animals showed that the increase in specific activity of CYP is related to high content of apoenzymes. We showed for the first time that rats and rabbits are characterized by interspecies differences in the induction of cytochrome P450 isoforms under the influence of triphenyldioxane.