The study investigates the molecular mechanisms by which rifampin induces expression of the *MDR1* gene, which encodes intestinal P-glycoprotein (P-gp). P-gp plays a crucial role in the absorption and presystemic elimination of many xenobiotics. The researchers used the human colon carcinoma cell line LS174T, which is highly inducible by rifampin, to study this process. They identified a cluster of nuclear receptor response elements at about −8 kb upstream of the *MDR1* gene, containing several binding sites for the nuclear receptor PXR (pregnane X receptor). Among these, only one DR4 motif was necessary for induction by rifampin. Electrophoretic mobility shift assays and reporter gene assays confirmed that PXR binds specifically to this DR4 motif as a heterodimer with RXRα. Co-transfection experiments with an expression plasmid for hPXR demonstrated that PXR mediates induction of MDR1 through this enhancer element. The findings suggest that a similar mechanism, involving PXR binding to nuclear response elements, is responsible for the induction of both CYP3A4 and MDR1 by xenobiotics. This study provides insights into the regulation of *MDR1* expression and highlights the role of PXR in this process.The study investigates the molecular mechanisms by which rifampin induces expression of the *MDR1* gene, which encodes intestinal P-glycoprotein (P-gp). P-gp plays a crucial role in the absorption and presystemic elimination of many xenobiotics. The researchers used the human colon carcinoma cell line LS174T, which is highly inducible by rifampin, to study this process. They identified a cluster of nuclear receptor response elements at about −8 kb upstream of the *MDR1* gene, containing several binding sites for the nuclear receptor PXR (pregnane X receptor). Among these, only one DR4 motif was necessary for induction by rifampin. Electrophoretic mobility shift assays and reporter gene assays confirmed that PXR binds specifically to this DR4 motif as a heterodimer with RXRα. Co-transfection experiments with an expression plasmid for hPXR demonstrated that PXR mediates induction of MDR1 through this enhancer element. The findings suggest that a similar mechanism, involving PXR binding to nuclear response elements, is responsible for the induction of both CYP3A4 and MDR1 by xenobiotics. This study provides insights into the regulation of *MDR1* expression and highlights the role of PXR in this process.