Many organisms respond to toxic compounds in their environment with the induction of regulatory networks controlling the expression and activity of cytochrome P450 monooxygenase (P450s) detoxificative enzymes. The black swallowtail caterpillar, Papilio polyxenes, responds to xanthotoxin, a toxic phytochemical ubiquitous in its hostplants, with the induction of transcription and expression of two P450s, CYP6B1 and CYP6B3, mediated by a number of elements within 150 nt of the transcription initiation site. One of these elements is the xenobiotic response element to xanthotoxin (XRE-xan), which lies upstream of the consensus response element to the aryl hydrocarbon receptor (XRE-AhR) and the octamer-1 binding site (OCT-1); these cis-elements are involved in the mammalian responses to polycyclic aryl hydrocarbons via the well-characterized aryl hydrocarbon response network. Transient transfection analyses conducted in Sf9 cells have indicated that both XRE-xan and XRE-AhR, but not OCT-1, are critical for constitutive as well as xanthotoxin- and benzo[α]pyrene-induced transcription from the CYP6B1v3 promoter. The CYP6B1v3 promoter is capable of responding to benzo[α]pyrene as well as xanthotoxin in transiently transfected Sf9 cells. Moreover, in this transient transfection system, the Drosophila homologues of mammalian AhR and its heterodimerization partner ARNT, spineless (Ss) and tango (Tgo), transcriptionally upregulate the CYP61v3 promoter for which XRE-AhR and XRE-Xan seem to be necessary. Based on these results, we propose a model in which the networks regulating responses to aryl hydrocarbons and xanthotoxin regulate this promoter.