Ligand binding by the aryl hydrocarbon receptor (AhR), a member of the bHLH-PAS family of transcriptional regulatory proteins, has been mapped to a region within the second 'PAS' domain, a conserved sequence motif first discovered in the Per-ARNT-Sim family of proteins. In addition to the bacterial photoactive yellow protein (PYP), which had been proposed as a structural prototype for the three dimensional fold of PAS domains, two crystal structures of the PAS domain have recently been determined: the human potassium channel HERG and the heme binding domain of the bacterial O(2) sensing FixL protein. The three structures reveal a highly conserved structural framework in evolutionary rather distant PAS domains, provide a more general view of how these domains can recognize their ligands and suggest a structure-function relationship that we exploited to build a three-dimensional model of the ligand binding domain (LBD) of the mouse aryl hydrocarbon receptor (mAhR). The model allowed us to putatively identify the residues responsible for the recognition of polychlorinated dibenzo-p-dioxins (PCDDs) by AhR receptors and to formulate an hypothesis on the signal transduction mechanism.