Bcl-xL is a member of the Bcl-2 family of proteins that regulates outer mitochondrial membrane permeability. Bcl-xL is an antiapoptotic member that prevents release of cytochrome c from the mitochondria intermembrane space into the cytosol. Bcl-xL is present on the outer mitochondrial membrane and is also found on other membranes in some cell types. Natural Bcl-xL contains a carboxylterminal mitochondria targeting sequence. Recombinant Bcl-xL missing the mitochondrial targeting sequence maintains its ability to neutralize proapoptotic Bcl-2 family members. Neutralization by Bcl-xL appears to be through binding the BH3 region of proapoptotic Bcl-2 family members. This activity does not require the mitochondrial targeting sequence.