Quantitative changes in cytochrome P450 proteins involved in drug metabolism as a consequence of drug treatment are important parameters in predicting the fates and pharmacological consequences of xenobiotics and drugs. In this study we undertake comparative P450 proteomics using liver from control and 1,4 bis 2-(3,5-dichloropyridyloxybenzene) (TCPOBOP)-dosed mice. The method involved separation of microsomal proteins by SDS-PAGE, trypsin digestion and post-digest ¹⁸O/¹⁶O-labelling, followed by nano-liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for peptide identification, and LC-MS for relative quantification. Seventeen P450 proteins were identified from mouse liver, of which sixteen yielded data sufficient for relative quantification. All the P450s detected were unambiguously identified, with the exception of the highly homologous CYP2A4/2A5. With the exception of CYP2A12, 2D10 and 2F2, the levels of all the P450s quantified were affected by treatment with TCPOBOP (3 mg/kg). CYP1A2, 2A4/5, 2B10, 2B20, 2C29, 2C37, 2C38, 3A11 and 39A1 were upregulated, and CYP2C40, 2E1, 3A41 and 27A1 downregulated. The response of CYP2B20 to stimulation has not previously been distinguished from that of CYP2B10 because of the poor discrimination between these two proteins (they share 87% sequence identity). Differential response to chemical stimulation by closely related members of the CYP2C subfamily was also observed.