2,3,7,8-tetrachlorodibenzo-p-dioxin (TODD) is one of the most toxic environmental pollutants that causes various biological effects on mammals. To identify the genes involved in hepatotoxicity and hepatocarcinogenesis induced by TODD, we have conducted here serial analysis of gene expression of mouse liver 7 days after treatment with a single oral dose of 20 jig TCDD/kg body weight. We have sequenced total of 113,067 tags, including 56,420 tags and 56,647 tags from normal liver and TODD-treated liver library, respectively. Statistical analysis showed that TODD significantly altered 346 transcripts (p < 0.05) including 94 ESTs. The genes regulated by TCDD were not only the genes encoding drug metabolizing enzymes and stress response genes but also a wide variety of genes encoding cytoskeleton related proteins, signal transduction, and plasma proteins. This comprehensive gene expression analysis would provide novel genes that may help to clarify the mechanism of TCDD effects on mammalian liver, and also give a new approach for prevention and treatment. (C) 2002 Elsevier Science (USA).