CD97 is a member of a new subgroup of seven-span transmembrane (7-TM) molecules which belong to the secretin receptor superfamily. Different from other members of the secretin receptor family, these recently characterized molecules have extended extracellular regions comprising several EGF domains near the NH2 terminus. We recently demonstrated that the extracellular part of CD97 is involved in intercellular adhesion since it specifically binds to CD55 (decay accelerating factor), a regulatory protein of the complement cascade. To our knowledge this is the first demonstration of a cellular ligand for a 7-TM molecule.