comparative analysis of dioxin response elements in human mouse and rat genomic sequences comparative approaches were used to identify human mouse and rat dioxin response elements dres in genomic sequences unambiguously assigned to a nucleotide refseq accession number a total of 13 bona fide dres all including the substitution intolerant core sequence gcgtg and adjacent variable sequences were used to establish a position weight matrix and a matrix similarity ms score threshold to rank identified dres dres with ms scores above the threshold were disproportionately distributed in close proximity to the transcription start site in all three species gene expression assays in hepatic mouse tissue confirmed the responsiveness of 192 genes possessing a putative dre previously identified functional dres in wellcharacterized ahrregulated genes including cyp1a1 and cyp1b1 were corroborated putative dres were identified in 48 out of 2437 humanmouserat orthologous genes between 1500 and the transcriptional start site of which 19 of these genes possessed positionally conserved dres as determined by multiple sequence alignment seven of these nineteen genes exhibited 2378tetrachlorodibenzopdioxinmediated regulation although there were significant discrepancies between in vivo and in vitro results interestingly of the mouserat orthologous genes with a dre between 1500 and 1500 only 37 had an equivalent human ortholog these results suggest that ahrmediated gene expression may not be well conserved across species which could have significant implications in human risk assessment