Cytochrome c induces fusion of phosphatidylserine /phosphatidylethanolamine vesicles while apocytochrome c does not have a fusogenic capability despite the fact that the apoprotein binds to the vesicles more extensively. In order to see whether the difference in the fusogenic behavior comes from the topological variation in membrane bound proteins, the holoprotein and apoprotein were labeled with phenylisothiocyanate, a hydrophobic label, in the presence of its hydrophilic analogue p-sulfophenylisothiocyanate. Apocytochrome c was labeled with the hydrophobic probe more extensively than the cytochrome c, indicating that the apoprotein penetrates deeper into the bilayer than cytochrome c does. The translocation experiments of these proteins by trypsin entrapped vesicles further supported this conclusion.