P-glycoprotein, the MDR1 gene product which confers multidrug resistance to tumor cells and transports cationic or neutral compounds with high lipophilicity outward from the cells, excretes xenobiotics into the lumen in the kidney, small intestine and liver. The expression of P-glycoprotein is enhanced by stresses including exposure to various xenobiotics, while the activity is regulated to some extent by the phosphorylation. P-glycoprotein and P450 3A have similar substrate specificities and inducers, which may suggest they have complementary roles in the liver. The other subclass, MDR3, which does not show the multidrug resistance, translocates phosphatidyl choline selectively into the outer leaflet of the liver canalicular membrane, and may protect the liver from the detergent effect of bile acids.