Induction of mouse cytochrome P450 2A5 (CYP2A5) during hepatotoxicity is related to altered cellular redox, however the molecular mechanism is not known. Expression of CYP2A5 is induced by phenobarbital by a transcriptional mechanism. This study investigated the transcriptional regulation of CYP2A5 expression by altered cellular redox and phenobarbital. Alteration of cellular redox by DTTox, menadione, nitrofurantoin, and 't'-butylhydroperoxide increased 'Cyp2a5' promoter activity, however not to the extent that CYP2A5 mRNA expression was increased during altered cellular redox, indicating that post-transcriptional mechanisms may also be involved. Increased ' Cyp2a5' promoter activity following phenobarbital treatment correlated well with increased CYP2A5 mRNA expression. The 'Cyp2a5' promoter region was not transactivated by mCAR and mutation of the putative CAR/PXR half-site did not affect promoter activity. The CAR antagonist androstenol did not inhibit 'Cyp2a5' promoter activity. The phenobarbital-mediated increase in activity of the proximal 3 kb region of the 'Cyp2a5' promoter is not dependent on CAR.